| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute Bacterial Sinusitis |
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| E.1.1.1 | Medical condition in easily understood language |
| Acute Bacterial Sinusitis |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate the efficacy of intranasal MFNS as an adjunctive treatment to antibiotic therapy in acute episodes of bacterial sinusitis. Efficacy is to be determined by the change from Baseline in AM/PM PRIOR major symptoms score (MSS) minus sinus headache averaged over Days 1 to 29 and the change in percentage of opacification of one maxillary sinus (the one with the highest percentage of opacification) as compared to antibiotic treatment alone. |
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| E.2.2 | Secondary objectives of the trial |
| To evaluate safety using vital signs, laboratory test results, and subject-reported adverse events. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. A subject must be 12 years of age and older, of either sex, and of any race.
2. A subject must weigh at least 40 kg (88 lb).
3. A subject (and/or parent/guardian) must be willing to give written informed consent and able to adhere to dose and visit schedules.
4. A subject must have a clinical diagnosis of acute bacterial sinusitis:
•The current acute episode must be of at least moderate severity, as assessed by the subject at the Screening Visit (overall condition scale of 0 = none, 1 = mild, 2 = moderate, and 3 = severe).
•There must have been a symptom-free period prior to this acute episode, as determined by subject history
5. A subject must be symptomatic at the Screening Visit, as follows:
Symptoms of sinusitis must be present for at least 5 but no more than 21 days as determined by subject history.
•A subject-evaluated PRIOR At least two symptoms of the MSS must be of moderate or greater severity (score ≥2).
•Purulent rhinorrhea and facial pain/pressure/tenderness must be present (score ≥1).
6. A subject must have radiographic evidence of sinusitis on CT scans taken at Screening, to include opacification of at least 10% in at least one of the maxillary sinuses.
7. A subject must be symptomatic at the Baseline Visit, as follows:
•The five twice-daily (AM and PM) run-in diary reflective (PRIOR) MSS, which consist of the 2 days prior to the Baseline Visit and the AM score at the Baseline Visit must total at least 30.
•Purulent rhinorrhea and facial pain/pressure/tenderness must be present (score ≥1), and at least two symptoms must be of moderate or greater severity (score ≥2), at the Baseline Day 1 AM evaluation.
8. A subject 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.
9. A subject’s clinical laboratory tests (hematology, blood chemistry, and urinalysis), vital signs, and 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.
10. 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. Postmenopausal women will be exempted from the use of contraception during the study.
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| E.4 | Principal exclusion criteria |
1. 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.
2. A subject with a history of chronic sinusitis (symptoms lasting greater than 3 months) or having undergone sinus or nasal surgery for chronic sinusitis or nasal polyps.
3. A subject with a history of symptomatic seasonal allergic rhinitis (SAR) who, during the study period, are living in or traveling to locations where the allergen to which they are allergic is present.
4. A subject with glaucoma or a history of posterior subcapsular cataracts.
5. A 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.
6. A subject who fails to observe the medication washout times outlined in the protocol prior to Screening.
7. A subject with an allergy to corticosteroids or penicillins. A thorough history is to be taken and recorded on the source record.
8. A subject who has used any investigational drug within 30 days of Screening.
9. A subject with a concurrent need for antibiotic therapy other than study drug (amoxicillin/clavulanic acid).
10. A subject who is anticipating sinus or nasal surgery within the next month.
11. A subject who has been previously randomized into this study.
12. A subject who 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.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
•The change from Baseline in AM/PM PRIOR MSS minus sinus headache averaged over Days 1 to 29.
•The change in percent of opacification of the maxillary sinus.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Subjects assessed and recorded the severity of their symptoms of sinusitis twice daily (in the morning [AM] and in the evening [PM]) during study. |
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| E.5.2 | Secondary end point(s) |
Subanalysis Endpoint:
•Overall Treatment Effect Scale at Days 15 and 29 (results to be used to determine the MID of the MSS in subanalysis).
Additional Secondary Endpoints:
•Change from Baseline AM/PM PRIOR TSS and MSS averaged over Days 1 to 29.
•Change from Baseline AM PRIOR, AM NOW, PM PRIOR, PM NOW, AM/PM NOW TSS, MSS, and MSS minus sinus headache for Days 1 to 29.
•Change from Baseline AM PRIOR, AM NOW, PM PRIOR, PM NOW, AM/PM PRIOR, AM/PM NOW TSS,
MSS, and MSS minus sinus headache for each of Days 1, 2, 3, and 4, by week, and at Days 30 to 43.
•Change from Baseline AM PRIOR, AM NOW, PM PRIOR, PM NOW, AM/PM PRIOR, AM/PM NOW individual
symptom scores for each of Days 1, 2, 3, 4, by week, Days 1 to 29, and Days 30 to 43.
•Change from Baseline in Rhino QOL scores at Days 15 and 29 (the last treatment visit).
•Change from Baseline for each of the following sinus scores at Day 43 (or the last day in follow-up): the right
and left frontal, anterior ethmoid, posterior ethmoid, and sphenoid; the Ostiomeatal Complex; the least severe maxillary sinus at Baseline, and the sum of the maxillary sinuses.
•Change from Baseline in AM, PM, and AM/PM PNIF for each of Days 1, 2, 3, 4, by week, Days 1 to 29, and Days 30 to 43.
•Change from Baseline interference with daily activities for each of Days 1, 2, 3, 4, by week, Days 1 to 29, and Days 30 to 43.
•Change from Baseline Interference with sleep for each of Days 2, 3, 4, by week, Days 1 to 29, and Days 30 to 43.
•Subject evaluation of the overall condition of sinusitis at Days 15, 29, and Endpoint (the last treatment visit).
•Subject evaluation of therapeutic response at Days 15, 29, and Endpoint.
•Investigator evaluation of the overall condition of sinusitis at Days 15, 29, and Endpoint.
•Investigator evaluation of therapeutic response at Days 15, 29, and Endpoint.
•Proportion of treatment failures during the Treatment Period.
•Proportion of recurrences during the Follow-up Period.
•Adverse events, vital signs, and laboratory tests summarized by treatment group.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall Treatment Effect Scale at Days 15 and 29 (results to be used in the calculation of the minimum important difference [MID] of the MSS under a separate subanalysis
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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