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Study of an Investigational Nasal Aerosol or Placebo in Children (Ages 4 to 11) With Perennial Allergic Rhinitis (PAR)

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ClinicalTrials.gov Identifier: NCT01783548
Recruitment Status : Completed
First Posted : February 5, 2013
Results First Posted : October 12, 2015
Last Update Posted : October 12, 2015
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Allergic Rhinitis
Interventions Drug: BDP Nasal Aerosol
Drug: Placebo
Enrollment 547
Recruitment Details  
Pre-assignment Details A total of 770 subjects were screened. The 547 participants were randomly assigned to either BDP nasal aerosol (80 mcg/day) or placebo nasal aerosol in a 2:1 ratio.
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Hide Arm/Group Description BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period. Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period.
Period Title: Overall Study
Started 362 [1] 185 [1]
Full Analysis Set (FAS) 358 184
Completed 328 167
Not Completed 34 18
Reason Not Completed
Adverse Event             8             4
Withdrawal by Subject             11             8
Non-compliance             4             0
Protocol Violation             2             2
Lost to Follow-up             8             3
Lack of Efficacy             1             1
[1]
Randomized
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol Total
Hide Arm/Group Description BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period. Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period. Total of all reporting groups
Overall Number of Baseline Participants 362 185 547
Hide Baseline Analysis Population Description
Intent to treat population which included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 362 participants 185 participants 547 participants
8.0  (2.16) 8.0  (2.23) 8.0  (2.18)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 362 participants 185 participants 547 participants
4 to 5 years 62 31 93
6 to 11 years 300 154 454
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 185 participants 547 participants
Female
175
  48.3%
71
  38.4%
246
  45.0%
Male
187
  51.7%
114
  61.6%
301
  55.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 362 participants 185 participants 547 participants
White 272 145 417
Black 65 25 90
Other 25 15 40
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 362 participants 185 participants 547 participants
Hispanic or Latino 144 75 219
Not Hispanic or Latino 217 110 327
Unknown 1 0 1
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 362 participants 185 participants 547 participants
33.4  (13.40) 33.8  (13.24) 33.5  (13.34)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 362 participants 185 participants 547 participants
18.6  (4.22) 18.9  (4.33) 18.7  (4.25)
1.Primary Outcome
Title Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age
Hide 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 and the during study rTNSS values were defined as the average AM and PM subject-reported rTNSS during each time period.

Time Frame Baseline (Day -4 to Day 1 predose), Day 1 (postdose) to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of randomized study medication and had at least 1 post-baseline subject-reported rTNSS assessment. Subpopulation of study participants aged 6-11 years.
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Hide Arm/Group Description:
BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period.
Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period.
Overall Number of Participants Analyzed 296 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.26  (0.12) -1.60  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BDP Nasal Aerosol 80 mcg/Day, Placebo Nasal Aerosol
Comments Based on other studies, the standard deviation for the change from baseline over the first 6 weeks of treatment in the average of AM and PM rTNSS is assumed to be 2.0. Using this standard deviation, 450 subjects aged 6 to 11 years (300 on active treatment of BDP and 150 on placebo) provide approximately 90% power to detect a difference of 0.65 in rTNSS change from baseline between treatment groups with a two-sided alpha level of 0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
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 -0.66
Confidence Interval (2-Sided) 95%
-1.08 to -0.24
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 6 To 11 Years Of Age
Hide 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 and the during study iTNSS values were defined as the average AM and PM subject-reported iTNSS during each time period.

Time Frame Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). Subpopulation of study participants aged 6-11 years.
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Hide Arm/Group Description:
BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period.
Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period.
Overall Number of Participants Analyzed 296 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.98  (0.12) -1.39  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BDP Nasal Aerosol 80 mcg/Day, Placebo Nasal Aerosol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
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 -0.58
Confidence Interval (2-Sided) 95%
-0.99 to -0.18
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Reflective Total Nasal Symptom Score (rTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age
Hide 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 and the during study rTNSS values were defined as the average AM and PM subject-reported rTNSS during each time period.

Time Frame Baseline (Day -4 to Day 1 predose), Day 1 (postdose) to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of randomized study medication and had at least 1 post-baseline subject-reported rTNSS assessment.
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Hide Arm/Group Description:
BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period.
Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period.
Overall Number of Participants Analyzed 358 184
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.32  (0.11) -1.71  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BDP Nasal Aerosol 80 mcg/Day, Placebo Nasal Aerosol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
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 -0.62
Confidence Interval (2-Sided) 95%
-1.00 to -0.23
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Average Morning (AM) and Evening (PM) Subject-Reported Instantaneous Total Nasal Symptom Score (iTNSS) Over The First 6 Weeks Of Treatment In Subjects 4 To 11 Years Of Age
Hide 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 and the during study iTNSS values were defined as the average AM and PM subject-reported iTNSS during each time period.

Time Frame Baseline (Day -4 to Day 1 predose), Days 1 (postdose) to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of randomized study medication and had at least 1 post-baseline subject-reported rTNSS assessment.
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Hide Arm/Group Description:
BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period.
Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period.
Overall Number of Participants Analyzed 358 184
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.07  (0.11) -1.53  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BDP Nasal Aerosol 80 mcg/Day, Placebo Nasal Aerosol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
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 -0.54
Confidence Interval (2-Sided) 95%
-0.91 to -0.17
Estimation Comments [Not Specified]
Time Frame Day 1 to Week 16
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Hide Arm/Group Description BDP nasal aerosol: 80 mcg dose once daily in the morning. Participants/parents administer 40 mcg BDP (one spray per nostril) during the 12-week Treatment Period. Placebo nasal aerosol: Participants/parents administer placebo (no medication) (one spray per nostril) once daily in the morning during the 12-week Treatment Period.
All-Cause Mortality
BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Affected / at Risk (%) Affected / at Risk (%)
Total   0/362 (0.00%)   0/185 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BDP Nasal Aerosol 80 mcg/Day Placebo Nasal Aerosol
Affected / at Risk (%) Affected / at Risk (%)
Total   33/362 (9.12%)   21/185 (11.35%) 
Nervous system disorders     
Headache  1  16/362 (4.42%)  14/185 (7.57%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  18/362 (4.97%)  8/185 (4.32%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT01783548     History of Changes
Other Study ID Numbers: BDP-AR-306
First Submitted: January 31, 2013
First Posted: February 5, 2013
Results First Submitted: July 27, 2015
Results First Posted: October 12, 2015
Last Update Posted: October 12, 2015