Study to Evaluate the Safety and Tolerability of a Nasal Spray in Patients With Chronic Allergic or Nonallergic Rhinitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00783432

Recruitment Status : Completed

First Posted : October 31, 2008

Results First Posted : October 2, 2009

Last Update Posted : October 6, 2009

Sponsor:

Information provided by:

Meda Pharmaceuticals

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Chronic Allergic Rhinitis Nonallergic Rhinitis
Interventions	Drug: Astepro Nasal Spray (0.1% azelastine hydrochloride) Drug: Astelin Nasal Spray (0.1% azelastine hydrochloride)
Enrollment	862

Participant Flow

Recruitment Details	First observation 24 July 2006 and last observation 28 Dec 2007
Pre-assignment Details	Subjects participated in a one-week screening period to identify appropriate subjects based on symptom scores


Arm/Group Title	Astepro Nasal Spray	Astelin Nasal Spray
Arm/Group Description	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Arm/Group Description	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Period Title: Overall Study
Started	430 ^[1]	432 ^[1]
Completed	345	354
Not Completed	85	78
Reason Not Completed
Adverse Event	22	17
Lack of Efficacy	20	21
Lost to Follow-up	11	6
Withdrawal by Subject	23	20
subject moved	3	5
Protocol Violation	6	9
[1] This includes 2 subjects that received a randomization number but did not receive study drug

Baseline Characteristics

Arm/Group Title		Astepro Nasal Spray	Astelin Nasal Spray	Total
Arm/Group Description		(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)	Total of all reporting groups
Arm/Group Description		(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)	Total of all reporting groups
Overall Number of Baseline Participants		428	430	858
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	428 participants	430 participants	858 participants
	<=18 years	11 2.6%	10 2.3%	21 2.4%
	Between 18 and 65 years	389 90.9%	391 90.9%	780 90.9%
	>=65 years	28 6.5%	29 6.7%	57 6.6%
Age Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	428 participants	430 participants	858 participants
		41.2 (14.95)	41.3 (15.12)	41.2 (15.03)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	428 participants	430 participants	858 participants
	Female	221 51.6%	236 54.9%	457 53.3%
	Male	207 48.4%	194 45.1%	401 46.7%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	428 participants	430 participants	858 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	8 1.9%	16 3.7%	24 2.8%
	Native Hawaiian or Other Pacific Islander	1 0.2%	0 0.0%	1 0.1%
	Black or African American	6 1.4%	4 0.9%	10 1.2%
	White	410 95.8%	405 94.2%	815 95.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	3 0.7%	5 1.2%	8 0.9%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	428 participants	430 participants	858 participants
Australia		40	39	79
Europe		388	391	779
Duration of Rhinitis Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	428 participants	430 participants	858 participants
		10.5 (11.04)	11.3 (10.85)	10.9 (10.95)
Total Nasal Symptom Score (AM + PM) ^[1] Mean (Standard Deviation) Unit of measure: Units on a scale (0-3)
	Number Analyzed	428 participants	430 participants	858 participants
		9.69 (4.506)	9.96 (4.725)	9.82 (4.617)
		[1] Measure Description: TNSS scale: 0=no symptoms, 1=mild symptoms, 2=moderate symptoms and 3 = severe symptoms scored twice daily such that the maximum daily score is 24.

Outcome Measures

1.Primary Outcome


Title	Number of Participants Reporting Adverse Events
Description	An AE can be any unfavorable and unintended sign,symptom, or disease t...
Description	An AE can be any unfavorable and unintended sign,symptom, or disease temporally associated with the use of this investigational product, whether or not considered related to the investigational product. An AE is any untoward medical occurrence in a subject which does not necessarily have a causal relationship with this treatment.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Number of participants for analysis was based on a safety population that included any subject who received at least one dose of study medication.


Arm/Group Title	Astepro Nasal Spray	Astelin Nasal Spray
Arm/Group Description:	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Arm/Group Description:	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Overall Number of Participants Analyzed	428	430
Measure Type: Number Unit of Measure: Participants
	207	211

2.Primary Outcome


Title	Focused Examination of the Head and Neck With Findings Recorded on a Numeric Scale.
Description	Examination of head and neck(scale: 0, 1+=Mild, 2+=Moderate, 3++Severe...
Description	Examination of head and neck(scale: 0, 1+=Mild, 2+=Moderate, 3++Severe) for mucosal edema, nasal discharge, mucosal erythema, mucosal bleeding, mucosal ulcerations, crusting of mucosa, conjunctiva, tympanic membranes, lymph nodes of head and neck. Direct visual nasal examination (scale: None, Grade 2, Grade 3, and Grade 4) for epistaxis,ulceration and pain.
Time Frame	baseline and 12 months/ET

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Astepro Nasal Spray	Astelin Nasal Spray
Arm/Group Description:	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Arm/Group Description:	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Overall Number of Participants Analyzed	428	430
Measure Type: Number Unit of Measure: Participants
Conjunctiva: Total baseline	428	430
Conjunctiva: baseline-None	264	254
Conjunctiva: baseline-Mild (1+)	99	109
Conjunctiva: baseline-Moderate (2+)	53	54
Conjunctiva: baseline-Severe (3+)	12	13
Conjunctiva: Total M12/ET	414	417
Conjunctiva: M12/ET-None	366	363
Conjunctiva: M12/ET-Mild (1+)	44	43
Conjunctiva: M12/ET-Moderate (2+)	4	11
Conjunctiva:M12/ET-Severe (3+)	0	0
Tympanic membranes: Total baseline	428	430
Tympanic membranes: baseline-None	342	344
Tympanic membranes: baseline-Mild (1+)	60	62
Tympanic membranes:baselineModerate (2+)	21	17
Tympanic membranes: baseline-Severe (3+)	5	7
Tympanic membranes: Total M12/ET	414	417
Tympanic membranes: M12/ET-None	405	408
Tympanic membranes:M12/ET-Mild (1+)	8	5
Tympanic membranes: M12/ET-Moderate (2+)	1	4
Tympanic membranes:M12/ET Severe (3+)	0	0
Lymphadenopathy: Total baseline	428	430
Lymphadenopathy: baseline-None	389	393
Lymphadenopathy: baseline-Mild (1+)	32	27
Lymphadenopathy: baseline-Moderate (2+)	7	7
Lymphadenopathy: baseline-Severe (3+)	0	3
Lymphadenopathy: Total M12/ET	414	417
Lymphadenopathy: M12/ET-None	408	407
Lymphadenopathy:M12/ET-Mild (1+)	6	10
Lymphadenopathy:M12/ET-Moderate (2+)	0	0
Lymphadenopathy: M12/ET-Severe (3+)	0	0
Mucosal edema: Total baseline	428	430
Mucosal edema: baseline-None	32	30
Mucosal edema: baseline-Mild (1+)	91	80
Mucosal edema: baseline-Moderate (2+)	191	200
Mucosal edema: baseline-Severe (3+)	114	120
Mucosal edema: Total M12/ET	414	417
Mucosal edema:M12/ET-None	160	147
Mucosal edema: M12/ET-Mild (1+)	176	182
Mucosal edema: M12/ET-Moderate (2+)	69	76
Mucosal edema: M12/ET-Severe (3+)	9	12
Nasal discharge: Total baseline	428	430
Nasal discharge: baseline-None	40	44
Nasal discharge: baseline-Mild (1+)	113	109
Nasal discharge: baseline-Moderate (2+)	179	183
Nasal discharge: baseline-Severe (3+)	96	94
Nasal discharge: Total M12/ET	414	417
Nasal discharge:M12/ET-None	178	173
Nasal discharge: M12/ET-Mild (1+)	188	183
Nasal discharge: M12/ET-Moderate (2+)	46	54
Nasal discharge:M12/ET-Severe (3+)	2	7
Mucosal erythema: Total baseline	428	430
Mucosal erythema: baseline-None	80	82
Mucosal erythema: baseline-Mild (1+)	120	112
Mucosal erythema: baseline-Monderate (2+)	171	178
Mucosal erythema: baseline-Severe (3+)	57	58
Mucosal erythema: Total M12/ET	414	417
Mucosal erythema: M12/ET-None	213	221
Mucosal erythema: M12/ET-Mild (1+)	152	153
Mucosal erythema: M12/ET-Moderate (2+)	45	35
Mucosal erythema:M12/ET-Severe (3+)	4	8
Mucosal bleeding: Total baseline	428	430
Mucosal bleeding: baseline-None	362	376
Mucosal bleeding: baseline-Mild (1+)	56	51
Mucosal bleeding: baseline-Moderate (2+)	10	2
Mucosal bleeding: baseline-Severe (3+)	0	1
Mucosal bleeding: Total M12/ET	414	417
Mucosal bleeding: M12/ET-None	402	403
Mucosal bleeding: M12/ET-Mild (1+)	11	10
Mucosal bleeding: M12/ET-Moderate (2+)	1	4
Mucosal bleeding: M12/ET-Severe (3+)	0	0
Mucosal ulcerations: Total baseline	428	430
Mucosal ulcerations: baseline-None	348	362
Mucosal ulcerations: baseline-Mild (1+)	48	37
Mucosal ulcerations: baseline-Moderate (2+)	26	25
Mucosal ulcerations: baseline-Severe (3+)	6	6
Mucosal ulcerations: Total M12/ET	414	417
Mucosal ulcerations: M12/ET-None	401	404
Mucosal ulcerations: M12/ET-Mild (1+)	11	10
Mucosal ulcerations: M12/ET-Moderate (2+)	2	3
Mucosal ulcerations: M12/ET-Severe (3+)	0	0
Crusting of mucosa: Total baseline	428	430
Crusting of mucosa: baseline-None	293	311
Crusting of mucosa: baseline-Mild (1+)	86	75
Crusting of mucosa: baseline-Moderate (2+)	36	35
Crusting of mucosa: baseline-Severe (3+)	13	9
Crusting of mucosa: Total M12/ET	414	417
Crusting of mucosa: M12/ET-None	387	382
Crusting of mucosa: M12/ET-Mild (1+)	24	32
Crusting of mucosa: M12/ET-Moderate (2+)	3	3
Crusting of mucosa:M12/ET-Severe (3+)	0	0
Epistaxis: Total baseline	428	430
Epistaxis: baseline None	402	416
Epistaxis: baseline Grade 2	26	12
Epistaxis: baseline Grade 3	0	1
Epistaxis: baseline Grade 4	0	1
Epistaxis:Total M12/ET	414	417
Epistaxis: M12/ET None	413	415
Epistaxis: M12/ETGrade 2	1	2
Epistaxis:M12/ET Grade 3	0	0
Epistaxis: M12/ETGrade 4	0	0
Ulceration: Total baseline	428	430
Ulceration: baseline None	365	373
Ulceration: baseline Grade 2	63	57
Ulceration: baseline Grade 3	0	0
Ulceration: baseline Grade 4	0	0
Ulceration: Total M12/ET	413	417
Ulceration:M12/ET None	404	411
Ulceration: M12/ET Grade 2	8	6
Ulceration: M12/ET Grade 3	1	0
Ulceration: M12/ET Grade 4	0	0
Pain: Total baseline	428	430
Pain: baseline None	377	382
Pain: baseline Grade 2	38	28
Pain: baseline Grade 3	6	17
Pain: baseline Grade 4	7	3
Pain: Total M12/ET	413	417
Pain: M12/ET None	401	409
Pain: M12/ET Grade 2	10	6
Pain: M12/ET Grade 3	2	2
Pain: M12/ET Grade 4	0	0

3.Secondary Outcome


Title	Adult Mini-Rhinoconjuctivitis Quality of Life Questionnaire. Change From Baseline in RQLQ Score at Months 1,3,6,9 and 12/or Early Termination.
Description	The RQLQ consists of 7 domains rated on a 7-point scale with 0 being n...
Description	The RQLQ consists of 7 domains rated on a 7-point scale with 0 being not troubled by the allergy symptoms,and 6 being extremely troubled. Total possible RQLQ score is 42 at any given evaluation. Scale of how troubled is:0=Not,2=Somewhat,3=Moderate,4=Quite a bit,5=Very,6 Extremely. Only change from baseline to month 12 primary analysis is provided.
Time Frame	baseline, months 1,3,6,9 and 12/or early termination

Outcome Measure Data

Analysis Population Description

Analysis is based on safety population, which is defined as subjects who took at least one dose of study medication.


Arm/Group Title	Astepro Nasal Spray	Astelin Nasal Spray
Arm/Group Description:	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Arm/Group Description:	(0.1% azelastine hydrochloride)	(0.1% azelastine hydrochloride)
Overall Number of Participants Analyzed	428	430
Least Squares Mean (Standard Deviation) Unit of Measure: Units on a scale
Baseline	2.25 (1.103)	2.18 (1.050)
Month 1	-0.77 (1.007)	-0.83 (0.959)
Month 3	-1.00 (1.063)	-1.00 (1.048)
Month 6	-1.04 (1.206)	-0.94 (1.230)
Month 9	-1.09 (1.228)	-1.16 (1.197)
Month 12/Early termination	-0.88 (1.385)	-0.90 (1.339)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Astepro Nasal Spray, Astelin Nasal Spray
	Comments	Sample size was based on ICH Guideline E1:The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions. Comparisons performed using ANCOVA with baseline as a covariate. The model included treatment group and country as fixed effects to estimate least squares means.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.368
	Comments	This is the Baseline P-Value
	Method	ANOVA
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Astepro Nasal Spray, Astelin Nasal Spray
	Comments	Sample size was based on ICH Guideline E1:The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions. Comparisons performed using ANCOVA with baseline as a covariate. The model included treatment group and country as fixed effects to estimate least squares means.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.327
	Comments	This P-Value if for Month 1
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Astepro Nasal Spray, Astelin Nasal Spray
	Comments	Sample size was based on ICH Guideline E1:The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions. Comparisons performed using ANCOVA with baseline as a covariate. The model included treatment group and country as fixed effects to estimate least squares means.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.991
	Comments	This P-Value is for Month 3
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Astepro Nasal Spray, Astelin Nasal Spray
	Comments	Sample size was based on ICH Guideline E1:The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions. Comparisons performed using ANCOVA with baseline as a covariate. The model included treatment group and country as fixed effects to estimate least squares means.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.168
	Comments	This P-Value is for Month 6
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Astepro Nasal Spray, Astelin Nasal Spray
	Comments	Sample size was based on ICH Guideline E1:The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions. Comparisons performed using ANCOVA with baseline as a covariate. The model included treatment group and country as fixed effects to estimate least squares means.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.319
	Comments	This P-Value is for Month 9
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Astepro Nasal Spray, Astelin Nasal Spray
	Comments	Sample size was based on ICH Guideline E1:The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions. Comparisons performed using ANCOVA with baseline as a covariate. The model included treatment group and country as fixed effects to estimate least squares means.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.725
	Comments	This P-Value is for Month 12/ET
	Method	ANCOVA
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Astepro Nasal Spray		Astelin Nasal Spray
Arm/Group Description	(0.1% azelastine hydrochloride)		(0.1% azelastine hydrochloride)
Arm/Group Description	(0.1% azelastine hydrochloride)		(0.1% azelastine hydrochloride)
All-Cause Mortality
	Astepro Nasal Spray		Astelin Nasal Spray
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Astepro Nasal Spray		Astelin Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7		10
Cardiac disorders
Battery change for internal cardiac defibrillator ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Exacerbation angina pectoris ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Central Chest Pain ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Gastrointestinal disorders
Upper Abdominal Colic ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Infections and infestations
Sialoadenitis ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Acute Pyelonephritis ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Pneumonia Chlamidalis ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Injury, poisoning and procedural complications
Knee traumatism ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Fracture left foot ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Broken nose ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Musculoskeletal and connective tissue disorders
Exacerbation right shoulder pain ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Total right hip replacement ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal Carcinoma ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Basal Cell Carcinoma ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Prostate cancer ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Nervous system disorders
Syncope ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Pregnancy, puerperium and perinatal conditions
Spontaneous Abortion ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Renal and urinary disorders
Removal of bladder stones ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Reproductive system and breast disorders
Ovarian Cyst ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/428 (0.23%)	1	0/430 (0.00%)	0
Exertional dyspnoea ^† 1	0/428 (0.00%)	0	1/430 (0.23%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Astepro Nasal Spray		Astelin Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	163		146
Infections and infestations
Nasopharyngitis ^*	34/428 (7.94%)	34	25/430 (5.81%)	25
Nervous system disorders
Headache ^*	49/428 (11.45%)	49	43/430 (10.00%)	43
Dysgeusia ^*	28/428 (6.54%)	28	32/430 (7.44%)	32
Respiratory, thoracic and mediastinal disorders
Epistaxis ^*	29/428 (6.78%)	29	32/430 (7.44%)	32
Pharyngolaryngeal Pain ^*	23/428 (5.37%)	23	14/430 (3.26%)	14
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

For multicenter studies, joint publication is required to assure that the initial publication is based on all data from all sites and investigators participating in these studies agree not to present data gathered individually or by subgroup centers before the initial publication unless jointly agreed by all other investigators and the Sponsor. Authorship will be determined by mutual agreement.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	William Wheeler, PhD
Organization:	Meda Pharmaceuticals
Phone:	732-564-2351
EMail:	wwheeler@medapharma.us

Layout table for additonal information

Responsible Party:	Harry Sacks, MD, Vice President, Medical and Scientific Affairs
ClinicalTrials.gov Identifier:	NCT00783432
Other Study ID Numbers:	MP432
First Submitted:	October 30, 2008
First Posted:	October 31, 2008
Results First Submitted:	December 29, 2008
Results First Posted:	October 2, 2009
Last Update Posted:	October 6, 2009

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