Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Adult and Adolescent Subjects With Perennial Allergic Rhinitis (PAR)

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01133626
• Collaborator: (none)
• Enrollment: 107
• Locations: 3
• Arms: 3
• Duration (Months): 3
• Patients Per Site: 35.7
• Patients Per Site Per Month: 11.8

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the effects of BDP HFA Nasal Aerosol on HPA-axis function.

Condition or Disease	Intervention/Treatment	Phase
Perennial Allergic Rhinitis	Drug: Placebo Nasal Aerosol; Drug: Prednisone capsules; Drug: Placebo Prednisone Capsules; Drug: Beclomethasone dipropionate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group, 6-Week Study Designed to Investigate the Effects of BDP HFA Nasal Aerosol on the Hypothalamic-Pituitary-Adrenal (HPA) Axis When Administered in Adolescent and Adult Subjects (12 to 45 Years of Age) With Perennial Allergic Rhinitis (PAR)
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Drug: Placebo Nasal Aerosol; Placebo nasal aerosol administered daily for 42 days of treatment; Drug: Placebo Prednisone Capsules; Placebo prednisone capsule taken each day on the last 7 days of treatment
Experimental: BDP HFA 320 µg/day Participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily each morning for 6 weeks (42 days). During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Drug: Placebo Prednisone Capsules; Placebo prednisone capsule taken each day on the last 7 days of treatment; Drug: Beclomethasone dipropionate; Total daily dose of 320 micrograms per day of beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) applied as a nasal aerosol each morning for 42 days.; Other Names: QNASL(TM)
Active Comparator: Prednisone Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a 10/mg a day prednisone capsule.	Drug: Placebo Nasal Aerosol; Placebo nasal aerosol administered daily for 42 days of treatment; Drug: Prednisone capsules; Prednisone 10 mg capsule taken each day on the last 7 days of treatment

Outcome Measures

Primary Outcome Measures

1. The 24-hour Serum Cortisol Weighted Mean After 42 Days of Treatment [Day 0 (Baseline), Day 42]

   Geometric mean serum cortisol weighted mean values were calculated at baseline and after 6 weeks (42 days) of treatment. The geometric mean ratio of week 6 / baseline is reported. The primary outcome compares the BDP HFA and Placebo treatment arms. The comparison of active control (Placebo/Prednisone) and Placebo treatment arms is an "other pre-specified" outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed Consent

• Male or female subjects 12-45 years of age

• Documented history of perennial allergic rhinitis

• General good health

• Other criteria apply

Exclusion Criteria:

• History of physical findings of nasal pathology (within 60 days prior to Screening Visit 1)

• Participation in any investigational drug study 30 days preceding Screening Visit 1

• History of respiratory infection/disorder with 14 days preceding Screening Visit 1

• Use of any prohibited concomitant medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Clinical Study Site	North Dartmouth	Massachusetts	United States	02747
2	Teva Clinical Study Site	New Braunfels	Texas	United States	78130
3	Teva Clinical Study Site	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Sudeesh K. Tantry, Ph.D., Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01133626
• Other Study ID Numbers: BDP-AR-304
• First Posted: May 31, 2010
• Last Update Posted: Jul 4, 2012
• Last Verified: May 1, 2012

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Prednisone; Beclomethasone

Study Results

Participant Flow

Recruitment Details	A total of 139 patients were screened and 128 patients were enrolled in the study and participated in the Run-in Period. Of the 128 enrolled patients, 107 were randomized to study treatment.
Pre-assignment Detail	During the 7 to 14 day Run-in Period (prior to randomization), participants self-administered a single-blind placebo nasal aerosol once daily in the morning.

Arm/Group Title	BDP HFA 320 µg/Day	Placebo	Placebo/Prednisone
Arm/Group Description	Participants self-administered 4 actuations (two per nostril) of 80 µg beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) once daily each morning for 6 weeks (42 days). During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a 10/mg a day prednisone capsule.
Period Title: Overall Study
STARTED	50	46	11
Safety Population	50	46	11
Per Protocol Population	48	41	9
COMPLETED	49	41	9
NOT COMPLETED	1	5	2

Baseline Characteristics

Arm/Group Title	BDP HFA 320 µg/Day	Placebo	Placebo/Prednisone	Total
Arm/Group Description	Participants self-administered 4 actuations (two per nostril) of 80 µg beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) once daily each morning for 6 weeks (42 days). During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a 10/mg a day prednisone capsule.	Total of all reporting groups
Overall Participants	48	41	9	98
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.3 (10.0)	26.6 (10.6)	26.2 (11.9)	27.4 (10.4)
Sex: Female, Male (Count of Participants)
Female	25 52.1%	22 53.7%	7 77.8%	54 55.1%
Male	23 47.9%	19 46.3%	2 22.2%	44 44.9%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	18 37.5%	17 41.5%	2 22.2%	37 37.8%
Not Hispanic or Latino	30 62.5%	24 58.5%	7 77.8%	61 62.2%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%	0 0%	1 11.1%	1 1%
Asian	1 2.1%	0 0%	0 0%	1 1%
Black or African American	7 14.6%	2 4.9%	1 11.1%	10 10.2%
White	42 87.5%	38 92.7%	7 77.8%	87 88.8%
Unknown or Not Reported	0 0%	1 2.4%	0 0%	1 1%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.9 (7.9)	27.0 (6.2)	28.4 (7.9)	27.6 (7.2)

Outcome Measures

1. Primary Outcome

Title	The 24-hour Serum Cortisol Weighted Mean After 42 Days of Treatment
Description	Geometric mean serum cortisol weighted mean values were calculated at baseline and after 6 weeks (42 days) of treatment. The geometric mean ratio of week 6 / baseline is reported. The primary outcome compares the BDP HFA and Placebo treatment arms. The comparison of active control (Placebo/Prednisone) and Placebo treatment arms is an "other pre-specified" outcome.
Time Frame	Day 0 (Baseline), Day 42

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	BDP HFA 320 µg/Day	Placebo	Placebo/Prednisone
Arm/Group Description	Participants self-administered 4 actuations (two per nostril) of 80 µg beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) once daily each morning for 6 weeks (42 days). During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.	Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a 10/mg a day prednisone capsule.
Measure Participants	48	41	9
Geometric Mean (Standard Error) [ratio]	0.90 (1.04)	0.95 (1.03)	0.31 (1.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BDP HFA 320 µg/Day, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority would be demonstrated if the lower limit of a two-sided 95% CI for the geometric mean ratio of BDP HFA 320 mcg/day to placebo was greater than 0.80.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric mean ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	BDP HFA 320 µg/Day		Placebo		Placebo/Prednisone
Arm/Group Description	Participants self-administered 4 actuations (two per nostril) of 80 µg beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) once daily each morning for 6 weeks (42 days). During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.		Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a placebo capsule as double-blind therapy for prednisone.		Participants self-administered 4 actuations (two per nostril) of placebo HFA once daily each morning for 6 weeks (42 days) as double-blind therapy for BDP. During week 6 (days 36-42), participants also took a 10/mg a day prednisone capsule.
All Cause Mortality
	BDP HFA 320 µg/Day		Placebo		Placebo/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BDP HFA 320 µg/Day		Placebo		Placebo/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/46 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	BDP HFA 320 µg/Day		Placebo		Placebo/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/50 (6%)		3/46 (6.5%)		5/11 (45.5%)
Infections and infestations
Gastroenteritis	0/50 (0%)		0/46 (0%)		1/11 (9.1%)
Investigations
Blood oestrogen increased	0/50 (0%)		0/46 (0%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	0/50 (0%)		0/46 (0%)		1/11 (9.1%)
Epistaxis	2/50 (4%)		1/46 (2.2%)		1/11 (9.1%)
Nasal discomfort	1/50 (2%)		2/46 (4.3%)		1/11 (9.1%)

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.