Sinusitis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Nasonex® (mometasone furoate nasal spray), when used together with an antibiotic, for the relief of symptoms associated with acute bacterial sinusitis. Efficacy will be based on both subjective (assessment of symptom severity by the patient) and objective measurements (computed tomography \[CT\] imaging of the sinuses).
Interventions
DRUGMFNS and antibiotic
MFNS BID for 29 days plus amoxicillin/clavulanic acid BID for 10 days
DRUGMatching Placebo nasal spray plus antibiotic
Matching placebo nasal spray BID for 29 days plus amoxicillin/clavulanic acid BID for 10 days
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be 12 years of age and older, of either sex, and of any race. * Must weigh at least 40 kg (88 lb). * Must be willing to give written informed consent and be able to adhere to dose and visit schedules. * Must have a clinical diagnosis of acute bacterial sinusitis. * Must be symptomatic at the Screening and Baseline Visits on the basis of subject assessments of major symptoms score. * Must have radiographic evidence of sinusitis on CT scans taken at Screening. * Must be in general good health and free of any clinically significant disease (other than sinusitis) that would interfere with the study schedule or procedures, or compromise the subject's safety. * A subject's clinical laboratory tests (hematology, blood chemistry, and urinalysis), vital signs, and electrocardiogram (ECG) recordings must be within normal limits or clinically acceptable to the investigator/qualified designee. Any test results that are questionable should be referred to the sponsor. * A female subject of child-bearing potential must have a negative serum pregnancy (beta-hCG) test at Screening. She must agree to use a medically accepted method of contraception throughout the entire study period. Postmenopausal women will be exempted from the use of contraception during the study. Documented absence of menses for at least 1 year will indicate that a female is postmenopausal. If a pre-menarche female subject begins menstruating during the study, a serum pregnancy test must be done at the next visit. A female subject of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study.
Exclusion criteria
* A subject with moderate to severe persistent asthma that requires daily treatment with inhaled steroids, or an exacerbation of asthma within the past 30 days. * A history of chronic sinusitis (symptoms lasting greater than 3 months) or having undergone sinus or nasal surgery for chronic sinusitis or nasal polyps. * A history of symptomatic seasonal allergic rhinitis and who, during the study period, is living in or traveling to locations where the allergen to which he/she is allergic is present. * Subject with glaucoma or a history of posterior subcapsular cataracts. * Subject with nasal polyps visible upon physical examination, immotile cilia syndrome, immunodeficiency disease, cystic fibrosis, clinically significant cardiovascular (including rheumatic heart disease), pulmonary, renal, hepatic, metabolic, hematological or neurologic disease that in the investigator's judgment might interfere with the evaluation of the therapy, or subjects who are immunocompromised, in renal failure, or on dialysis. * Subject fails to observe the medication washout times outlined in the protocol prior to Screening. * Subject has an allergy to corticosteroids or penicillins. * Subject has used any investigational drug within 30 days of Screening. * Subject has a concurrent need for antibiotic therapy other than study drug (amoxicillin/clavulanic acid). * Subject is anticipating sinus or nasal surgery within the next month. * Subject has been previously randomized into this study. * Subject is part of the staff personnel directly involved with the study or is a family member of the investigational study staff involved in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | 29-day Treatment Period and 2-week no-treatment Follow-up Period. | The least squares mean decrease from Baseline in AM/PM PRIOR MSS, excluding sinus headache, averaged over Days 1 to 29. PRIOR is the subject's status over the previous 12 hours (reflective). The MSS was defined as the sum of the following subject-evaluated symptoms: facial pain/pressure/tenderness, sinus headache, purulent rhinorrhea, post-nasal drip, and nasal stuffiness/congestion.MSS scores are as follows: 0=none, 1=mild, 2=moderate, 3=severe for each individual symptom. |
| Change From Baseline to Endpoint in Percent of Opacification of the Maxillary Sinus That Had the Maximum Opacification Score at Baseline | 29-day Treatment Period and 2-week no-treatment Follow-up Period. | A coronal computerized tomography was obtained to visulaize all nasal sinuses and the ostiomeatal complex. Opacification was measured as a percentage of the area of the sinus that was occupied by either fluid or mucosal thickening. The change in percentage of opacification of one maxillary sinus (the one with the highest percentage of opacification) as compared to antibiotic treatment alone. The percentage of opacification was measured and the change from baseline for that percentage was reported. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mometasone Furoate Nasal Spray (MFNS) Mometasone furoate nasal spray (MFNS) twice daily (BID) for 29 days, plus antibiotic for 10 days (amoxicillin 875 mg/clavulanic acid 125 mg BID for participants 12 to 15 years of age or amoxicillin 2 gm/clavulanic acid 125 mg BID for participants 16 years of age or older). | 114 |
| Placebo Matching placebo nasal spray BID for 29 days, plus antibiotic for 10 days (amoxicillin 875 mg/clavulanic acid 125 mg BID or amoxicillin 2 gm/clavulanic acid 125 mg BID, depending on age). | 123 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 |
| Overall Study | Did not meet protocol eligibility | 2 | 4 |
| Overall Study | Lost to Follow-up | 4 | 7 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Treatment Failure | 1 | 6 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Mometasone Furoate Nasal Spray (MFNS) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Categorical >=65 years | 3 Participants | 10 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 107 Participants | 213 Participants |
| Age, Continuous | 39.3 years STANDARD_DEVIATION 13.2 | 39.0 years STANDARD_DEVIATION 14.9 | 39.2 years STANDARD_DEVIATION 14.1 |
| Sex: Female, Male Female | 80 Participants | 72 Participants | 152 Participants |
| Sex: Female, Male Male | 34 Participants | 51 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 114 | 17 / 123 |
| serious Total, serious adverse events | 0 / 114 | 1 / 123 |
Outcome results
Primary
Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29.
The least squares mean decrease from Baseline in AM/PM PRIOR MSS, excluding sinus headache, averaged over Days 1 to 29. PRIOR is the subject's status over the previous 12 hours (reflective). The MSS was defined as the sum of the following subject-evaluated symptoms: facial pain/pressure/tenderness, sinus headache, purulent rhinorrhea, post-nasal drip, and nasal stuffiness/congestion.MSS scores are as follows: 0=none, 1=mild, 2=moderate, 3=severe for each individual symptom.
Time frame: 29-day Treatment Period and 2-week no-treatment Follow-up Period.
Population: Not every randomized subject had complete data therefore the number of participants analyzed and the number of participants in the participant flow do not match.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mometasone Furoate Nasal Spray (MFNS) | Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | Baseline | 8.57 Units on a scale | Standard Deviation 1.78 |
| Mometasone Furoate Nasal Spray (MFNS) | Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | Days 1-29 | -4.9 Units on a scale | Standard Deviation 2.69 |
| Mometasone Furoate Nasal Spray (MFNS) | Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | Days 30-43 (follow-up) | -6.59 Units on a scale | Standard Deviation 2.81 |
| Placebo | Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | Baseline | 8.78 Units on a scale | Standard Deviation 2.03 |
| Placebo | Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | Days 1-29 | -4.46 Units on a scale | Standard Deviation 2.54 |
| Placebo | Baseline Change in AM/PM PRIOR Major Symptoms Score (Mss) Minus Sinus Headache Averaged Over Days 1 to 29. | Days 30-43 (follow-up) | -5.77 Units on a scale | Standard Deviation 2.98 |
95% CI: [-1.14, 0.25]
95% CI: [-1.65, 0]
Primary
Change From Baseline to Endpoint in Percent of Opacification of the Maxillary Sinus That Had the Maximum Opacification Score at Baseline
A coronal computerized tomography was obtained to visulaize all nasal sinuses and the ostiomeatal complex. Opacification was measured as a percentage of the area of the sinus that was occupied by either fluid or mucosal thickening. The change in percentage of opacification of one maxillary sinus (the one with the highest percentage of opacification) as compared to antibiotic treatment alone. The percentage of opacification was measured and the change from baseline for that percentage was reported.
Time frame: 29-day Treatment Period and 2-week no-treatment Follow-up Period.
Population: Not every randomized subject had complete data therefore the number of participants analyzed and the number of participants in the participant flow do not match.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mometasone Furoate Nasal Spray (MFNS) | Change From Baseline to Endpoint in Percent of Opacification of the Maxillary Sinus That Had the Maximum Opacification Score at Baseline | Baseline | 50.7 Percentage of opacification | Standard Deviation 30.4 |
| Mometasone Furoate Nasal Spray (MFNS) | Change From Baseline to Endpoint in Percent of Opacification of the Maxillary Sinus That Had the Maximum Opacification Score at Baseline | Change from Baseline at Endpoint | -23.7 Percentage of opacification | Standard Deviation 35.2 |
| Placebo | Change From Baseline to Endpoint in Percent of Opacification of the Maxillary Sinus That Had the Maximum Opacification Score at Baseline | Baseline | 56.8 Percentage of opacification | Standard Deviation 31.7 |
| Placebo | Change From Baseline to Endpoint in Percent of Opacification of the Maxillary Sinus That Had the Maximum Opacification Score at Baseline | Change from Baseline at Endpoint | -32.5 Percentage of opacification | Standard Deviation 32 |
95% CI: [-0.5, 18.2]