Study of Mometasone Furoate Nasal Spray and Oxymetazoline Nasal Spray Given Together Once A Day To Treat Seasonal Allergic Rhinitis (P04500)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00552110
• Collaborator: Quintiles, Inc. (Industry)
• Enrollment: 707
• Arms: 5
• Duration (Months): 7.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of the combination of mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY) given together once a day in treating subjects with seasonal allergic rhinitis (SAR) in relieving symptoms including nasal congestion. The secondary objectives of this study are to evaluate the potential of the combination to produce tachyphylaxis and/or rebound congestion, and to evaluate the safety of the combination.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Allergic Rhinitis	Drug: OXY combination: mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY); Drug: OXY combination: mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY); Drug: mometasone furoate nasal spray (MFNS) once daily; Drug: oxymetazoline nasal spray (OXY) twice daily; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 707 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Concurrent Administration of Mometasone Furoate Nasal Spray (MFNS) and Oxymetazoline Nasal Spray Administered Once Daily (QD) vs. Oxymetazoline Twice Daily (BID), Mometasone Furoate QD, and Placebo in the Treatment of Subjects With Seasonal Allergic Rhinitis
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination1 Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily	Drug: OXY combination: mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY); MFNS 2 sprays per nostril with OXY 1 spray per nostril once daily x 2 weeks. Matching placebo to MFNS given every evening (PM).; Other Names: MFNS + OXY combination
Experimental: Combination3 MFNS with OXY 3 sprays once daily	Drug: OXY combination: mometasone furoate nasal spray (MFNS) and oxymetazoline nasal spray (OXY); MFNS 2 sprays per nostril with OXY 3 sprays per nostril once daily x 2 weeks. Matching placebo to MFNS given every evening.; Other Names: MFNS + OXY combination assessing a different dose (ie, number of sprays) from that used in Group 1
Active Comparator: Mometasone MFNS once daily	Drug: mometasone furoate nasal spray (MFNS) once daily; MFNS 2 sprays per nostril once daily x 2 weeks. Matching placebo to MFNS given every morning (AM) and every evening.; Other Names: MFNS QD
Active Comparator: Oxymetazoline OXY twice daily	Drug: oxymetazoline nasal spray (OXY) twice daily; OXY 2 sprays per nostril twice daily x 2 weeks. Matching placebo to MFNS given every morning.; Other Names: OXY BID
Placebo Comparator: Placebo Placebo nasal spray	Drug: Placebo; Matching placebo to MFNS given every morning and every evening x 2 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15 [15 days of treatment]

   Subjects scored severity of rhinorrhea, nasal congestion/stuffiness, nasal itching, and sneezing at the time of evaluation (NOW) using an ordinal scale from 0 = none to 3 = severe. Evaluations were performed daily in the morning (AM) and evening (PM). For each evaluation, individual symptom scores were summed to a TNSS, which was then averaged for a single score across the 15 day treatment period.

2. Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score [from baseline to hour 4 on Day 1]

   Subjects scored nasal congestion/stuffiness using an ordinal scale from 0 = none to 3 = severe. Baseline was the average of the scores assessed every 15 minutes for 1 hour prior to dosing on Day 1. After dosing on Day 1, congestion was scored every 15 minutes for the 1st hour and every 30 minutes for the next 3 hours. Area under the curve (AUC) was calculated using the trapezoid rule, then standardization achieved by dividing the calculation by 4 hours. Treatment comparisons were examined using the standardized AUC(0-4 hr) of the change from baseline to hour 4 on Day 1.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must be 12 years of age or older, of either sex, and of any race.

• Must have at least a 2-year documented history of SAR which exacerbates during the time period over which the subject will be participating.

• Must have a documented (within the past 12 months) positive skin-prick test response to an appropriate seasonal allergen appropriate to the geographical vicinity in which the study is being carried out and over the period of time the subject is participating.

• Must be clinically symptomatic at the Screening and Baseline Visits.

• Must be in general good health as confirmed by routine clinical and laboratory testing and electrocardiogram results.

• Must be free of any clinically significant disease, other than SAR, which would interfere with the study evaluations.

• Must be willing to give written informed consent and must be able to adhere to dosing and visit schedules and study requirements.

• Female subjects of child-bearing potential must have a negative serum pregnancy test at screening. Nonsterile and premenopausal female subjects must be using a medically acceptable method of birth control prior to screening and during the entire study.

• Must have the ability to transmit electronic diary data on a regular basis.

Exclusion Criteria:

• A subject with a history of anaphylaxis and/or other severe local reaction(s) to skin testing.

• A subject with asthma who requires chronic use of inhaled or systemic corticosteroids.

• A subject with current or history of frequent, clinically significant sinusitis or chronic purulent postnasal drip.

• A subject with rhinitis medicamentosa.

• A subject with glaucoma and/or increased intraocular pressure.

• A subject who has nasal structural abnormalities, including large nasal polyps and marked septal deviations, which significantly interfere with nasal air flow.

• A subject who, in the opinion of the investigator, is dependent on nasal, oral, or ocular decongestants, nasal topical antihistamines, or nasal steroids.

• A pregnant or nursing female.

• A subject with current evidence of clinically significant hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric, pulmonary, autoimmune disease, or other disease that precludes the subject's participation in the study. Particular attention should be given to exclude subjects with conditions that would currently interfere with the absorption, distribution, metabolism, or excretion of the study drug or interfere with the subject's ability to complete or reliably complete the diaries.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co
• Quintiles, Inc.

Investigators

• Study Director: Ariel A Teper, MD, Schering-Plough

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00552110
• Other Study ID Numbers: P04500
• First Posted: Nov 1, 2007
• Last Update Posted: Feb 11, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Mometasone Furoate; Phenylephrine; Oxymetazoline

Study Results

Participant Flow

Arm/Group Title	Combination1	Combination3	Mometasone	Oxymetazoline	Placebo
Arm/Group Description	Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily	MFNS with OXY 3 sprays once daily	MFNS once daily	OXY twice daily	Placebo nasal spray
Period Title: Overall Study
STARTED	146	139	139	141	142
COMPLETED	142	134	137	133	133
NOT COMPLETED	4	5	2	8	9

Baseline Characteristics

Arm/Group Title	Combination1	Combination3	Mometasone	Oxymetazoline	Placebo	Total
Arm/Group Description	Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily	MFNS with OXY 3 sprays once daily	MFNS once daily	OXY twice daily	Placebo nasal spray	Total of all reporting groups
Overall Participants	145	139	139	140	142	705
Age (Count of Participants)
<=18 years	8 5.5%	12 8.6%	5 3.6%	5 3.6%	12 8.5%	42 6%
Between 18 and 65 years	135 93.1%	124 89.2%	132 95%	131 93.6%	127 89.4%	649 92.1%
>=65 years	2 1.4%	3 2.2%	2 1.4%	4 2.9%	3 2.1%	14 2%
Sex: Female, Male (Count of Participants)
Female	93 64.1%	93 66.9%	101 72.7%	95 67.9%	89 62.7%	471 66.8%
Male	52 35.9%	46 33.1%	38 27.3%	45 32.1%	53 37.3%	234 33.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in AM/PM Instantaneous Total Nasal Symptom Score (NOW TNSS) Averaged Over Days 1 to 15
Description	Subjects scored severity of rhinorrhea, nasal congestion/stuffiness, nasal itching, and sneezing at the time of evaluation (NOW) using an ordinal scale from 0 = none to 3 = severe. Evaluations were performed daily in the morning (AM) and evening (PM). For each evaluation, individual symptom scores were summed to a TNSS, which was then averaged for a single score across the 15 day treatment period.
Time Frame	15 days of treatment

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT): all randomized subjects who had taken at least one dose of study drug

Arm/Group Title	Combination1	Combination3	Mometasone	Oxymetazoline	Placebo
Arm/Group Description	Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily	MFNS with OXY 3 sprays once daily	MFNS once daily	OXY twice daily	Placebo nasal spray
Measure Participants	145	138	139	139	140
Least Squares Mean (Standard Error) [units on a scale]	-3.29 (0.209)	-3.36 (0.216)	-2.97 (0.213)	-2.44 (0.215)	-1.90 (0.209)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination1, Oxymetazoline
	Comments	Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same mean change from baseline in AM/PM NOW TNSS as that of OXY twice daily. Power calculation: The target randomization of 875 subjects (175 subjects per treatment arm) was needed to detect a treatment difference of 0.8 point or more in change from baseline in AM/PM NOW TNSS, with a two-sided alpha of 0.05 and 90% power, assuming a pooled standard deviation of 2.3 points.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Multiplicity for multiple treatment comparisons was not adjusted.
	Method	ANCOVA
	Comments	Analysis of Covariance (ANCOVA); classification variables: treatment, center, dosing sequence (stratification variable); covariate: baseline score

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination3, Oxymetazoline
	Comments	Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same mean change from baseline in AM/PM NOW TNSS as that of OXY twice daily.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mometasone, Placebo
	Comments	Null hypothesis: the administration of MFNS once daily has the same mean change from baseline in AM/PM NOW TNSS as that of placebo.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Standardized Area Under the Curve From 0 to 4 Hours [AUC(0-4 hr)] of the Change From Baseline to Hour 4 on Day 1 in Nasal Congestion Score
Description	Subjects scored nasal congestion/stuffiness using an ordinal scale from 0 = none to 3 = severe. Baseline was the average of the scores assessed every 15 minutes for 1 hour prior to dosing on Day 1. After dosing on Day 1, congestion was scored every 15 minutes for the 1st hour and every 30 minutes for the next 3 hours. Area under the curve (AUC) was calculated using the trapezoid rule, then standardization achieved by dividing the calculation by 4 hours. Treatment comparisons were examined using the standardized AUC(0-4 hr) of the change from baseline to hour 4 on Day 1.
Time Frame	from baseline to hour 4 on Day 1

Outcome Measure Data

Analysis Population Description

Intention to treat: all randomized subjects who had taken at least one dose of study drug

Arm/Group Title	Combination1	Combination3	Mometasone	Oxymetazoline	Placebo
Arm/Group Description	Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily	MFNS with OXY 3 sprays once daily	MFNS once daily	OXY twice daily	Placebo nasal spray
Measure Participants	144	138	139	139	140
Least Squares Mean (Standard Error) [units on a scale]	-0.80 (0.056)	-0.92 (0.057)	-0.63 (0.057)	-1.06 (0.057)	-0.57 (0.056)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination1, Mometasone
	Comments	Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same standardized AUC(0-4 hr) of the change from baseline in nasal congestion score as that of MFNS once daily.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments	Multiplicity for multiple treatment comparisons was not adjusted.
	Method	ANCOVA
	Comments	ANCOVA; classification variables: treatment, center, dosing sequence (stratification variable); covariate: baseline score

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combination3, Mometasone
	Comments	Null hypothesis: the concurrent administration of MFNS and OXY once daily has the same standardized AUC (0-4hr) of the change from baseline in nasal congestion score as that of MFNS once daily
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline, Placebo
	Comments	Null hypothesis: the administration of OXY twice daily has the same standardized AUC(0-4 hr) of the change from baseline in nasal congestion score as that of placebo
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Combination1		Combination3		Mometasone		Oxymetazoline		Placebo
Arm/Group Description	Mometasone Furoate nasal spray (MFNS) with oxymetazoline nasal spray (OXY) 1 spray once daily		MFNS with OXY 3 sprays once daily		MFNS once daily		OXY twice daily		Placebo nasal spray
All Cause Mortality
	Combination1		Combination3		Mometasone		Oxymetazoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Combination1		Combination3		Mometasone		Oxymetazoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/145 (0%)		0/139 (0%)		1/139 (0.7%)		0/140 (0%)		1/142 (0.7%)
Gastrointestinal disorders
Gastrooesophageal Reflux Disease	0/145 (0%)	0	0/139 (0%)	0	0/139 (0%)	0	0/140 (0%)	0	1/142 (0.7%)	1
Oesophageal Haemorrhage	0/145 (0%)	0	0/139 (0%)	0	1/139 (0.7%)	1	0/140 (0%)	0	0/142 (0%)	0
Other (Not Including Serious) Adverse Events
	Combination1		Combination3		Mometasone		Oxymetazoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/145 (4.8%)		5/139 (3.6%)		10/139 (7.2%)		7/140 (5%)		8/142 (5.6%)
Nervous system disorders
Headache	7/145 (4.8%)	9	5/139 (3.6%)	5	10/139 (7.2%)	11	7/140 (5%)	8	8/142 (5.6%)	8

Limitations/Caveats

Subject symptom data were not collected during the post-treatment period. Thus, daily diary data for rebound congestion was not analyzed.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.