Clinical Trial Results:
Placebo-Controlled Study of Mometasone Furoate Nasal Spray (MFNS) 200 mcg QD in the Treatment of Seasonal Allergic Rhinitis
Summary
|
|
EudraCT number |
2014-004875-21 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
19 Jun 2007
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
01 Mar 2016
|
First version publication date |
15 Jul 2015
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
P05067
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00453063 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Merck Sharp & Dohme Corp.
|
||
Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
|
||
Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp, ClinicalTrialsDisclosure@merck.com
|
||
Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp, ClinicalTrialsDisclosure@merck.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
19 Jun 2007
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
19 Jun 2007
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
19 Jun 2007
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
This study is designed to assess the efficacy of mometasone furoate nasal spay (MFNS) once daily (QD) compared with placebo in subjects with seasonal allergic rhinitis (SAR) in reducing the total nasal symptom score (TNSS) and the total ocular symptom score (TOSS).
|
||
Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Mar 2007
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 426
|
||
Worldwide total number of subjects |
426
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
48
|
||
Adults (18-64 years) |
369
|
||
From 65 to 84 years |
9
|
||
85 years and over |
0
|
|
||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||
Screening details |
A total of 426 participants were randomized at 24 study centers in the US to the following treatments: MFNS 200 mcg QD (n=211) and placebo (n=215). | |||||||||||||||||||||
Period 1
|
||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Mometasone Furoate Nasal Spray (MFNS) | |||||||||||||||||||||
Arm description |
MFNS 200 mcg (two sprays in each nostril) once daily (QD) in the morning. Each spray is equal to 50 mcg. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
mometasone furoate
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
Nasonex, SCH 032088
|
|||||||||||||||||||||
Pharmaceutical forms |
Nasal spray
|
|||||||||||||||||||||
Routes of administration |
Intranasal use
|
|||||||||||||||||||||
Dosage and administration details |
50 mcg/spray, two sprays in each nostril once daily (ie, 200 mcg QD) in the morning
|
|||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||
Arm description |
Two sprays in each nostril once daily | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Nasal spray
|
|||||||||||||||||||||
Routes of administration |
Intranasal use
|
|||||||||||||||||||||
Dosage and administration details |
Two sprays in each nostril once daily in the morning
|
|||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mometasone Furoate Nasal Spray (MFNS)
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
MFNS 200 mcg (two sprays in each nostril) once daily (QD) in the morning. Each spray is equal to 50 mcg. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Two sprays in each nostril once daily | ||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Mometasone Furoate Nasal Spray (MFNS)
|
||
Reporting group description |
MFNS 200 mcg (two sprays in each nostril) once daily (QD) in the morning. Each spray is equal to 50 mcg. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Two sprays in each nostril once daily |
|
|||||||||||||||||||
End point title |
Change from Baseline in the Average AM Instantaneous (NOW) Total Nasal Symptom Score (TNSS) Averaged Over Days 2 to 15 | ||||||||||||||||||
End point description |
TNSS was defined as the sum of the following four nasal symptoms: rhinorrhea, nasal congestion/stuffiness, nasal itching, sneezing; each symptom scored on a scale of 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The best possible score on this scale is 0 and the worst possible score on this scale is 12.
Participants with a missing evaluation at a given visit or time point were not included in the analysis for that evaluation. This included participants without a baseline score for a given change-from-baseline evaluation.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Baseline to Day 15
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [1] - All randomized participants were to be included in the analysis (intent-to-treat principle). [2] - All randomized participants were to be included in the analysis (intent-to-treat principle). |
|||||||||||||||||||
Statistical analysis title |
Change from BL in AM NOW TNSS: Day 2-15 average | ||||||||||||||||||
Statistical analysis description |
The co-primary statistical comparison of the effects of MFNS in the reduction of TNSS was based on the comparison of MFNS versus placebo in the average AM change from Baseline (BL) in the instantaneous (NOW) scores over Days 2 to 15 at the two-sided alpha = 0.05. Least Squares (LS) means, pooled standard deviation, and 95% Confidence Intervals were obtained from an ANCOVA model with treatment and site effect with baseline TNSS as a covariate.
|
||||||||||||||||||
Comparison groups |
Mometasone Furoate Nasal Spray (MFNS) v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
422
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% |
|
|||||||||||||||||||
End point title |
Change from Baseline in the Average AM Instantaneous (NOW) Total Ocular Symptom Score (TOSS) Averaged Over Days 2 to 15 | ||||||||||||||||||
End point description |
TOSS was defined as the sum of the following three ocular symptoms: redness of eyes, itching/burning eyes, and tearing/watering eyes; each symptom scored on a scale of 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The best possible score on this scale is 0 and the worst possible score on this scale is 9.
Participants with a missing evaluation at a given visit or time point were not included in the analysis for that evaluation. This included participants without a baseline score for a given change-from-baseline evaluation.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Baseline to Day 15
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [3] - All randomized participants were to be included in the analysis (intent-to-treat principle). [4] - All randomized participants were to be included in the analysis (intent-to-treat principle). |
|||||||||||||||||||
Statistical analysis title |
Change from BL in AM NOW TOSS: Day 2-15 average | ||||||||||||||||||
Statistical analysis description |
The co-primary statistical comparison of the effects of MFNS in the reduction of TOSS was based on the comparison of MFNS versus placebo in the average AM change from BL in the instantaneous (NOW) scores over Days 2 to 15 at the two-sided alpha = 0.05. LS means, pooled standard deviation, and 95% Confidence Intervals were obtained from an ANCOVA model with treatment and site effect with baseline TOSS as a covariate.
|
||||||||||||||||||
Comparison groups |
Mometasone Furoate Nasal Spray (MFNS) v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
422
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.304 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% |
|
|||||||||||||||||||
End point title |
Change from Baseline in AM NOW Nasal Congestion Score (NCS) Averaged Over Days 2 to 15 | ||||||||||||||||||
End point description |
Nasal congestion was one of the symptoms measured in the TNSS and was scored on a scale of 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The best possible score on this scale is 0 and the worst possible score on this scale is 3.
Participants with a missing evaluation at a given visit or time point were not included in the analysis for that evaluation. This included participants without a baseline score for a given change-from-baseline evaluation.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline to Day 15
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [5] - All randomized participants were to be included in the analysis (intent-to-treat principle). [6] - All randomized participants were to be included in the analysis (intent-to-treat principle). |
|||||||||||||||||||
Statistical analysis title |
Change from BL in AM NOW NCS: Day 2-15 average | ||||||||||||||||||
Statistical analysis description |
LS means, pooled standard deviation, and 95% Confidence Intervals were obtained from an ANCOVA model with treatment and site effect with baseline Nasal Congestion Score as a covariate.
|
||||||||||||||||||
Comparison groups |
Mometasone Furoate Nasal Spray (MFNS) v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
422
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.004 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% |
|
|||||||||||||||||||
End point title |
Change from Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Total Score at Endpoint (last post baseline evaluation carried forward) | ||||||||||||||||||
End point description |
The RQLQ consisted of 28 items that fell into the following seven domains: activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional. Each of the items was scored from 0 = not troubled to 6 = extremely troubled, and the total of the seven domains was the primary focus of this quality of life evaluation. The best possible score on this scale is 0 and the worst possible score on this scale is 42. The Endpoint was the last post baseline evaluation carried forward and was Day 15 for the majority of the participants.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline to Day 15
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [7] - RQLQ tool only validated in participants ≥18 years of age, so only administered to this age group. [8] - RQLQ tool only validated in participants ≥18 years of age, so only administered to this age group. |
|||||||||||||||||||
Statistical analysis title |
Change from BL in RQLQ at Endpoint | ||||||||||||||||||
Statistical analysis description |
LS means, pooled standard deviation, and 95% Confidence Intervals were obtained from an ANCOVA model with treatment and site effect with baseline RQLQ as a covariate.
|
||||||||||||||||||
Comparison groups |
Mometasone Furoate Nasal Spray (MFNS) v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
371
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.063 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% |
|
|||||||||||||||||||
End point title |
Change from Baseline in AM Peak Nasal Inspiratory Flow (PNIF) Averaged Over Days 2 to 15 | ||||||||||||||||||
End point description |
Participants were to measure nasal airflow twice daily (in the morning prior to study drug dosing and in the evening) using their PNIF meter. The highest of 3 assessments was to be recorded in the electronic diary. The PNIF meter limits were between 30 and 370 liters/minute. Normal values range between 100 and 150 liters/minute. A positive change from Baseline correlates with improved nasal air flow.
Participants with a missing evaluation at a given visit or time point were not included in the analysis for that evaluation. This included participants without a baseline score for a given change-from-baseline evaluation.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline to Day 15
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [9] - All randomized participants were to be included in the analysis (intent-to-treat principle). [10] - All randomized participants were to be included in the analysis (intent-to-treat principle). |
|||||||||||||||||||
Statistical analysis title |
Change from BL in PNIF: Day 2-15 average | ||||||||||||||||||
Statistical analysis description |
LS means, pooled standard deviation, and 95% Confidence Intervals were obtained from an ANCOVA model with treatment and site effect with baseline PNIF as a covariate.
|
||||||||||||||||||
Comparison groups |
Mometasone Furoate Nasal Spray (MFNS) v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
422
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.356 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% |
|
||||||||||||||||
Adverse events information [1]
|
||||||||||||||||
Timeframe for reporting adverse events |
From Day 1 up to 30 days after study completion/discontinuation (up to 45 days total)
|
|||||||||||||||
Adverse event reporting additional description |
All randomized participants were to be included in the analysis (intent-to-treat principle).
|
|||||||||||||||
Assessment type |
Systematic | |||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||
Dictionary version |
10
|
|||||||||||||||
Reporting groups
|
||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||
Reporting group description |
Two sprays in each nostril once daily | |||||||||||||||
Reporting group title |
Mometasone Furoate Nasal Spray (MFNS)
|
|||||||||||||||
Reporting group description |
MFNS 200 mcg (two sprays in each nostril) once daily (QD) in the morning. Each spray is equal to 50 mcg. | |||||||||||||||
|
||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
|
||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No adverse events were reported which exceeded the threshold of 5%. |
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
08 Mar 2007 |
The primary purpose of Amendment 1 (AM1) was to add TOSS as a co-primary endpoint and add change from baseline in AM PNIF (averaged over Days 2-15) as a key secondary endpoint. AM1 also reduced the planned total enrollment from 500 to 460, designated the Baseline Visit for investigator evaluation, revised inclusion criteria, specified an intent-to treat principle for efficacy analyses, and revised the statistical testing method of the co-primary endpoints. |
||
28 May 2007 |
The primary purpose of AM2 was to add secondary objectives and endpoints for RQLQ and AM NOW nasal congestion, and to clarify AEs and vital signs as Safety endpoints. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |