A Study to Evaluate the Safety and Effectiveness of a Nasal Spray to Treat Seasonal Allergies

• Sponsor: Meda Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00883168
• Collaborator: (none)
• Enrollment: 1,791
• Locations: 45
• Arms: 4
• Duration (Months): 3
• Patients Per Site: 39.8
• Patients Per Site Per Month: 13.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the combination of two allergy medications (formulated azelastine/fluticasone product)is more effective than placebo or either component medication alone (azelastine or fluticasone).

Condition or Disease	Intervention/Treatment	Phase
Seasonal Allergic Rhinitis	Drug: Placebo; Drug: azelastineHcl; Drug: fluticasone propionate; Drug: azelastine Hcl/fluticasone propionate	Phase 3

Detailed Description

This will be a Phase III, randomized, double-blind, placebo-controlled, parallel-group study in subjects with moderate-to-severe seasonal allergic rhinitis (SAR). The study will begin with a 7-day, single-blind, placebo lead-in period (Day -7 to Day 1). Subjects will be instructed to take placebo lead-in medication twice daily (1 spray per nostril), approximately every 12 hours. On Day 1, subjects who satisfy the symptom severity requirements and continue to meet all of the study inclusion/exclusion criteria will be randomized in a 1:1:1:1 ratio to receive 1 spray per nostril twice daily of MP29-02, azelastine hydrochloride, fluticasone propionate, or placebo nasal spray.

Efficacy will be assessed by the change from baseline in the subject-reported 12-hour reflective Total Nasal Symptom Score (TNSS). On Days 1 through 14, subjects will rate the instantaneous and reflective TNSS symptoms of sneezing, nasal congestion, runny nose, and nasal itching; the instantaneous and reflective total ocular symptom score (TOSS) symptoms of itchy eyes, watery eyes and eye redness; the symptom of postnasal drip will be reflectively, twice daily (AM and PM) in a diary prior to the dose of study medication. Symptoms will be scored on a 0 to 3 scale (0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms), such that the maximum daily symptom severity score will be 24 for the TNSS and 18 for the TOSS. Additional secondary efficacy variables will include reflective individual nasal and ocular symptom scores, as well as change from Baseline to Day 14 in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ).

Subjects ≥ 18 years of age will complete the RQLQ on Day 1 (prior to dosing) and Day 14. Subjects will return to the clinic on Day 7 for an interim evaluation. After completing the 2-week double-blind treatment period, subjects will return to the clinic on Day 14 (or at time of early termination) for an end-of-study evaluation. Safety and tolerability assessments will be made on Days 7 and 14. Tolerability will be evaluated by subject-reported adverse events (AEs), nasal examinations, and vital signs assessments

Study Design

• Study Type: Interventional
• Actual Enrollment: 1791 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind Trial of MP29-02 Nasal Spray Compared to Placebo, Azelastine Hydrochloride Nasal Spray and Fluticasone Propionate Nasal Spray in the Treatment of Patients With Seasonal Allergic Rhinitis
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo	Drug: Placebo; Placebo
Active Comparator: azelastine Hcl	Drug: azelastineHcl; azelastine hydrochloride 548 mg; Other Names: astelin
Active Comparator: fluticasone propionate	Drug: fluticasone propionate; fluticasone propionate 200 mcg
Experimental: azelastine Hcl /fluticasone propionate	Drug: azelastine Hcl/fluticasone propionate; azelastine hydrochloride 548 mcg/fluticasone propionate 200 mcg; Other Names: MP29-02

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS) [day 1 to day 14]

   change from baseline in 12-hour reflective total nasal symptom score (rTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period.The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.An greater negative value is suggestive of improvement.

Secondary Outcome Measures

1. Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS) [day 1 to day 14]

   change from baseline in 12-hour instantaneous total nasal symptom score (iTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period.The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.A greater negative score is suggestive of improved condition.

2. Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) [day 1 to day 14]

   adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scored at day 1(baseline) and at day 14.The scale is measured from a value of 0 to 24. A negative number corresponds to a change from baseline measurement. An increased negative number is suggestive of improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male/female subjects 12 years of age and older

2. Provide written informed consent/pediatric assent.

3. Subjects must have moderate-to-severe rhinitis, with one or more of the following present:

4. Sleep disturbance

5. Impairment of daily activities, leisure and/or sport

6. Impairment of school or work

7. Troublesome symptoms

8. Screening Visit: Have a 12-hour reflective TNSS of at least 8 out of a possible 12 and a congestion score of 2 or 3 on Visit 1

9. Randomization Visit: For the 3 days prior to Randomization and on the morning of Randomization, the sum of the 7 consecutive reflective AM and PM TNSS assessments shall be equal to or greater than 56, with a nasal congestion score equal to or greater than 14

10. Randomization Visit: instantaneous TNSS score of at least 8 and a congestion score of at least 2 just prior to beginning the onset of action assessment

11. Have taken at least 10 doses of the lead-in medication

12. Willing and able to comply with the study requirements

13. At least a 2-year history of SAR during the current allergy season

14. The presence of IgE-mediated hypersensitivity to a prevailing, individual, seasonal pollen, confirmed by a positive response to skin prick within the last year.

15. General good health and free of any disease or concomitant treatment that could interfere with the interpretation of the study results.

16. Subjects receiving immunotherapy injections (antigen desensitization) must be on a stable maintenance regimen for at least 30 days before the first study visit

17. Subjects currently receiving sublingual immunotherapy are excluded. A 6-month washout period is required following the last dose of sublingual immunotherapy.

Exclusion Criteria:

1. On Focused Nasal Examination, the presence of any superficial and moderate nasal mucosal erosion, nasal mucosal ulceration, or nasal septum perforation (Grade 1b - 4) at either the screening visit or randomization visit will disqualify the subject from the study.

2. Other nasal disease(s) likely to affect deposition of intranasal medication.

3. Nasal surgery or sinus surgery within the previous year.

4. Chronic sinusitis - more than 3 episodes per year

5. Planned travel outside of the pollen area during the study period

6. The use of any investigational drug within 30 days prior to Visit 1. No investigational products are permitted for use during the conduct of this study

7. Presence of any hypersensitivity to drugs similar to azelastine hydrochloride or fluticasone propionate

8. Women who are pregnant or nursing

9. Women of childbearing potential who are not abstinent or not practicing a medically acceptable method of contraception* see section 6.1.1

10. Respiratory Tract Infections within 14 days prior to Visit 1

11. Respiratory Tract Infections requiring antibiotic treatment 14 days prior to Visit 1

12. Asthma (with the exception of intermittent asthma).

13. Significant pulmonary disease including COPD

14. Clinically significant arrhythmia or symptomatic cardiac conditions

15. A known history of alcohol or drug abuse within the last 2 years

16. Existence of any surgical or medical condition or physical or laboratory findings, might significantly alter the absorption, distribution, metabolism, or excretion of study drug; that might significantly affect the subject's ability to complete this trial; or their safety in this trial.

17. Patients with a history of glaucoma

18. Clinically relevant abnormal physical findings within 1 week of randomization may preclude compliance with the study procedures

19. Employees of the research center or private practice and their family members

20. no more than 50% of their subjects have participated in protocol MP4001, MP4002 or MP4004

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allergy, Asthma and Immunology Associates	Scottsdale	Arizona	United States	85251
2	Clinical Research Center	Encinitas	California	United States	92024
3	AABI Associates Medical Group	Fountain Valley	California	United States	92708
4	Allergy & Asthma Care Center of So. Cal	Long Beach	California	United States	90808
5	Allergy Research Foundation	Los Angeles	California	United States	90025
6	Southern California Research	Mission Viejo	California	United States	92691
7	Allergy Associates Medical Group Inc	San Diego	California	United States	92120
8	Allergy and Asthma Medical Group and Research Center	San Diego	California	United States	92123
9	Bensch Research Associates	Stockton	California	United States	95207
10	Allergy and Asthma Clinical Research, Inc.	Walnut Creek	California	United States	94598
11	Asthma and Allergy Associates	Colorado Springs	Colorado	United States	80907
12	Storms Clinical Research Institute	Colorado Springs	Colorado	United States	80907
13	Colorado Allergy and Asthma Centers	Denver	Colorado	United States	80230
14	Clinical Research Atlanta	Atlanta	Georgia	United States	30342
15	Sneeze, Wheeze and Itch Associates	Normal	Illinois	United States	61761
16	Kansas City Allergy and Asthma	Overland Park	Kansas	United States	66210
17	Family Allergy and Asthma Reserach	Louisville	Kentucky	United States	40215
18	Northeast Medical Research Associates	North Dartmouth	Massachusetts	United States	02747
19	Clinical Reseacrh Institute	Minneapolis	Minnesota	United States	55402
20	The Clinical Research Center	St. Louis	Missouri	United States	63141
21	The Asthma and Allergy Center	Papillion	Nebraska	United States	68046
22	Atlantic Research Center	Ocean	New Jersey	United States	07712
23	Princeton Center for Clinical Research	Skillman	New Jersey	United States	08558
24	Research Asthma, Sinus and Allergy Centers	Warren	New Jersey	United States	07059
25	North Carolina Clinical Research	Raleigh	North Carolina	United States	27607
26	Bernstein Clinical Research Center	Cincinnati	Ohio	United States	45231
27	Allergy, Asthma and Clinical Research Center	Oklahoma City	Oklahoma	United States	73120
28	Clinical Research Institute of Southern Oregon, PC	Medford	Oregon	United States	97504
29	Allergy and Consultants of NJ/PA	Collegeville	Pennsylvania	United States	19426
30	Allergy and Clinical Immunology Associates	Pittsburgh	Pennsylvania	United States	15241
31	National Allergy, Asthma and Urticaria of Charleston	Charleston	South Carolina	United States	29407
32	East Tennesse Center for Clinical Research	Knoxville	Tennessee	United States	37909
33	Allergy and Asthma Associates	Austin	Texas	United States	78731
34	Allergy and Asthma Center of Austin	Austin	Texas	United States	78759
35	AARA Research Center	Dallas	Texas	United States	75231
36	Pharmaceutical Research & Consulting Inc	Dallas	Texas	United States	75231
37	Western Sky Medical Research	El Paso	Texas	United States	79902
38	Central Texas Health Research	New Braunfels	Texas	United States	78130
39	Diagnostic Research Group	San Antonio	Texas	United States	78229
40	Sylvana Research Associates	San Antonio	Texas	United States	78229
41	Allergy, Asthma Research Center	San Antonio	Texas	United States	78258
42	Allergy and Asthma Center	Waco	Texas	United States	76712
43	Allergy Asthma Research Institute	Waco	Texas	United States	76712
44	Intermountain Clinical Research	Draper	Utah	United States	84020
45	Asthma, Inc.	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Meda Pharmaceuticals

Investigators

• Study Director: Lewis M Fredane, MD, Meda Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Meda Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00883168
• Other Study ID Numbers: MP4006
• First Posted: Apr 17, 2009
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Fluticasone; Xhance; Azelastine

Study Results

Participant Flow

Arm/Group Title	MP29-02	Azelastine Hcl	Fluticasone Propionate	Placebo
Arm/Group Description	azelastine HCl 548mcg / fluticasone propionate 200mcg	azelastine HCl nasal spray	fluticasone propionate nasal spray	placebo nasal spray
Period Title: Overall Study
STARTED	448	445	450	448
COMPLETED	434	430	431	433
NOT COMPLETED	14	15	19	15

Baseline Characteristics

Arm/Group Title	MP29-02	Azelastine Hcl	Fluticasone Propionate	Placebo	Total
Arm/Group Description	azelastine HCl 548mcg / fluticasone propionate 200mcg	azelastine HCl nasal spray	fluticasone propionate nasal spray	placebo nasal spray	Total of all reporting groups
Overall Participants	448	445	450	448	1791
Age (Count of Participants)
<=18 years	57 12.7%	38 8.5%	56 12.4%	46 10.3%	197 11%
Between 18 and 65 years	382 85.3%	390 87.6%	390 86.7%	387 86.4%	1549 86.5%
>=65 years	9 2%	17 3.8%	4 0.9%	15 3.3%	45 2.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.6 (14.5)	36.4 (14.8)	34.2 (14.5)	34.7 (14.1)	35.2 (14.5)
Sex: Female, Male (Count of Participants)
Female	277 61.8%	271 60.9%	280 62.2%	269 60%	1097 61.3%
Male	171 38.2%	174 39.1%	170 37.8%	179 40%	694 38.7%
Region of Enrollment (participants) [Number]
United States	448 100%	445 100%	450 100%	448 100%	1791 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 12 Hour Reflective Total Nasal Symptom Score (rTNSS)
Description	change from baseline in 12-hour reflective total nasal symptom score (rTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period.The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.An greater negative value is suggestive of improvement.
Time Frame	day 1 to day 14

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population includes all subjects who had at least one post baseline dose efficacy evaluation

Arm/Group Title	MP29-02	Azelastine Hcl	Fluticasone Propionate	Placebo
Arm/Group Description	azelastine HCl 548mcg / fluticasone propionate 200mcg	azelastine HCl nasal spray	fluticasone propionate nasal spray	placebo nasal spray
Measure Participants	448	445	450	448
Least Squares Mean (Standard Deviation) [units on a scale]	-5.5 (5.2)	-4.8 (4.8)	-4.9 (4.7)	-3.4 (4.3)

2. Secondary Outcome

Title	Change From Baseline in 12 Hour Instantaneous Total Nasal Symptom Score (iTNSS)
Description	change from baseline in 12-hour instantaneous total nasal symptom score (iTNSS)consisting of nasal congestion,runny nose, itchy nose and sneezing scored twice daily (AM and PM) in diary cards for the entire 14 day study period.The measurement scale is 0 to 24.A reduction in symptom severity score is indicated by a negative value.A greater negative score is suggestive of improved condition.
Time Frame	day 1 to day 14

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population includes all subjects who received at least one post baseline efficacy evaluation

Arm/Group Title	MP29-02	Azelastine Hcl	Fluticasone Propionate	Placebo
Arm/Group Description	azelastine HCl 548mcg / fluticasone propionate 200mcg	azelastine HCl nasal spray	fluticasone propionate nasal spray	placebo nasal spray
Measure Participants	448	443	450	448
Least Squares Mean (Standard Deviation) [units on a scale]	-5.0 (5.3)	-4.3 (4.9)	-4.7 (4.9)	-3.1 (4.4)

3. Secondary Outcome

Title	Change From Baseline in Adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
Description	adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scored at day 1(baseline) and at day 14.The scale is measured from a value of 0 to 24. A negative number corresponds to a change from baseline measurement. An increased negative number is suggestive of improvement.
Time Frame	day 1 to day 14

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT)population includes all subjects(18 years or older) who had at least one post baseline efficacy evaluation

Arm/Group Title	MP29-02	Azelastine Hcl	Fluticasone Propionate	Placebo
Arm/Group Description	azelastine HCl 548mcg / fluticasone propionate 200mcg	azelastine HCl nasal spray	fluticasone propionate nasal spray	placebo nasal spray
Measure Participants	381	394	384	393
Least Squares Mean (Standard Deviation) [units on a scale]	-1.6 (1.3)	-1.4 (1.3)	-1.6 (1.2)	-1.0 (1.2)

Adverse Events

Arm/Group Title	MP29-02		Azelastine Hcl		Fluticasone Propionate		Placebo
Arm/Group Description	azelastine HCl 548mcg / fluticasone propionate 200mcg		azelastine HCl nasal spray		fluticasone propionate nasal spray		placebo nasal spray
All Cause Mortality
	MP29-02		Azelastine Hcl		Fluticasone Propionate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MP29-02		Azelastine Hcl		Fluticasone Propionate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/448 (0.2%)		0/449 (0%)		0/450 (0%)		1/451 (0.2%)
Infections and infestations
pyogenic arthritis right elbow	0/448 (0%)	0	0/449 (0%)	0	0/450 (0%)	0	1/451 (0.2%)	1
Injury, poisoning and procedural complications
lacerated right hand	1/448 (0.2%)	1	0/449 (0%)	0	0/450 (0%)	0	0/451 (0%)	0
Other (Not Including Serious) Adverse Events
	MP29-02		Azelastine Hcl		Fluticasone Propionate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/448 (12.7%)		47/449 (10.5%)		32/450 (7.1%)		26/451 (5.8%)
Gastrointestinal disorders
dysgusia	21/448 (4.7%)	21	23/449 (5.1%)	23	1/450 (0.2%)	1	0/451 (0%)	0
General disorders
oropharyngial pain	5/448 (1.1%)	5	2/449 (0.4%)	2	6/450 (1.3%)	6	2/451 (0.4%)	2
Infections and infestations
nasopharyngitis	3/448 (0.7%)	3	0/449 (0%)	0	3/450 (0.7%)	3	5/451 (1.1%)	5
Nervous system disorders
headache	10/448 (2.2%)	10	14/449 (3.1%)	14	8/450 (1.8%)	8	4/451 (0.9%)	4
somnolence	5/448 (1.1%)	5	2/449 (0.4%)	2	0/450 (0%)	0	1/451 (0.2%)	1
sinus headache	1/448 (0.2%)	1	0/449 (0%)	0	3/450 (0.7%)	3	5/451 (1.1%)	5
Respiratory, thoracic and mediastinal disorders
epistaxis	10/448 (2.2%)	10	6/449 (1.3%)	6	6/450 (1.3%)	6	8/451 (1.8%)	8
mucosal erosion	2/448 (0.4%)	2	0/449 (0%)	0	5/450 (1.1%)	5	1/451 (0.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigators participating in multicenter studies must agree not to present data gathered individually or by a subgroup of centers before the full, initial publication, unless this has been agreed to by all other investigators and Meda Pharmaceuticals. Meda Pharmaceuticals requests that it receive copies of any intended communication reasonably in advance (at least 15 working days for an abstract or oral presentation and 45 working days for a manuscript)