Rhinosinusitis
Conditions
Keywords
acute uncomplicated rhinosinusitis, acetylcysteine
Brief summary
The trial was conducted as a prospective, randomized, multinational, multicenter, double-blind study in 4 parallel groups of patients.
Detailed description
The study was the prospective, randomized, multinational, multicenter, double-blind study in 4 parallel groups of patients. Patients underwent screening examinations at Visit 1. Patients who met all inclusion/ no exclusion criteria were randomized at the baseline visit (Day 1) to the double-blind treatment for a duration of 14 days but in case of delayed final visit (Day 15) the patient could voluntarily take reserve study medication for a maximum of 3 additional days. After the end of the double-blind treatment phase, the patients underwent an end-of-treatment (EOT) examinations on Day 15 (+3). A follow-up phone call within 7 days after Day 15 (or earlier in case of premature termination) was performed.
Interventions
DRUGacetylcysteine
600 mg tablet
DRUGPlacebo
Placebo to acetylcysteine
Sponsors
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
14 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects aged between 14 and 75 years inclusive on the date of consent 2. Diagnosis of acute, uncomplicated rhinosinusitis defined at screening visit 1 and at Visit 2 as: 1. major symptom score (MSS) assessed by the patient ≥8 and ≤12 points for the following: rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure, whereupon the nasal congestion is mandatory and no more than 3 of the 5 symptoms are rated as severe 2. individual score for facial pain/pressure ≥1 (mild) and ≤2 (moderate) 3. presence of symptoms ≤3 days prior to screening visit 3. For adults (≥18 years): Informed consent to participate in the trial provided in written form; For adolescents (≥14 - \<18 years): own subject informed consent/ assent to participate in the trial and the informed consent from all parent(s)/ legal guardian(s) provided in written form.
Exclusion criteria
1. History of hypersensitivity or intolerance to the active substance or any of the excipients of the trial medication 2. Patient with history of hereditary fructose intolerance, galactose intolerance, lactase deficiency or glucose-galactose malabsorption 3. Chronic rhinosinusitis (symptoms lasting longer than 3 months) 4. Subjects who have undergone sinus or nasal surgery for chronic rhinosinusitis in the 6 months prior to screening visit 5. Sinus lavage within 7 days prior to screening visit 6. Odontogenic rhinosinusitis 7. Allergic (perennial or seasonal) rhinitis 8. Bronchial asthma or chronic obstructive pulmonary disease 9. Nasal polyposis or clinically relevant nasal septum deviation 10. Concomitant otitis 11. Intranasal or systemic use of corticosteroids within 30 days prior to screening visit 12. Intranasal or systemic use of antibiotics within 30 days prior to screening visit 13. Use of nasal decongestants within 2 days prior to screening visit 14. Concomitant treatment of common cold-like symptoms within 7 days prior to screening visit with any of the following: 1. Analgesics 2. Non-steroidal anti-inflammatory drugs 3. Antihistamines 15. Concomitant use of intranasal saline irrigation 16. Use of immunosuppressive agents within 30 days prior to screening visit 17. Immunocompromised state 18. Suspicion for acute bacterial rhinosinusitis (defined as presence of purulence for 3 to 4 days with fever ≥ 38.3°C) 19. Pregnant or breast-feeding female patient 20. Female patient of childbearing potential (not surgically sterilized/hysterectomized or postmenopausal for at least 1 year) who is not currently using (documented at screening visit) and not willing to use medically reliable methods of contraception for the entire trial duration such as oral, injectable or implantable contraceptives, intrauterine contraceptive devices (IUD), sexual abstinence or vasectomized partner 21. Any other condition of the patient (e.g. serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the trial treatment or may jeopardize patient's safety, compliance or adherence to protocol requirements 22. Participation in ANY research study involving another investigational medicinal product (IMP) within 30 days prior to screening visit, or simultaneous participation in another clinical study or previous participation in present study 23. Suspected alcohol/ drug dependence or abuse (including heavy smoking: ≥ 20 cigarettes daily) 24. Use of snuff tobacco 25. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial 26. Subjects who are known or suspected: * not to comply with the trial directives * not to be reliable or trustworthy * to be a dependent person, e.g. a relative, family member, or member/employee of the investigator's or sponsor's staff * subject is in custody or submitted to an institution due to a judicial order.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set | Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement. |
| Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set | Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement. |
| Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement. |
| Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Baseline (Day 1), Day 7 and Day 14 | SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. |
| Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Baseline (Day 1), Day 7 and Day 14 | SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. |
| Time to Onset of Action, Full Analysis Set | Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value\<0.05) improvement from placebo. |
| Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Baseline (Day 1), Day 7 and Day 14 | SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome. |
| Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4, 7, 10 and 15 | Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported. |
| Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4, 7, 10 and 15 | Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported. |
| Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Baseline (Day 1), Day 7 and Day 14 | SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome. |
| Time to Onset of Action, Per-Protocol Set | Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value\<0.05) improvement from placebo. |
Countries
Bulgaria, Germany, Moldova, Russia
Participant flow
Recruitment details
Participants were enrolled from 42 clinical centers located in Bulgaria, Germany, Moldova and Russia.
Pre-assignment details
Participants were randomized in 1:1:1:1 ratio
Participants by arm
| Arm | Count |
|---|---|
| Group A: 600 mg Acetylcysteine one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily) | 235 |
| Group B: 1200 mg Acetylcysteine two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily) | 238 |
| Group C: 2400 mg Acetylcysteine four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily) | 238 |
| Group D: Placebo four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily). | 233 |
| Total | 944 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 3 | 3 |
| Overall Study | Contact to subject lost | 0 | 0 | 0 | 1 |
| Overall Study | Exclusion criteria met | 1 | 2 | 0 | 2 |
| Overall Study | screening failure | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 0 | 2 |
Baseline characteristics
| Characteristic | Group C: 2400 mg Acetylcysteine | Group D: Placebo | Total | Group A: 600 mg Acetylcysteine | Group B: 1200 mg Acetylcysteine |
|---|---|---|---|---|---|
| Age, Continuous | 41.3 Years STANDARD_DEVIATION 13.1 | 41.1 Years STANDARD_DEVIATION 14 | 41.0 Years STANDARD_DEVIATION 13.6 | 41.0 Years STANDARD_DEVIATION 13.8 | 40.7 Years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Asian | 5 Participants | 2 Participants | 13 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 232 Participants | 231 Participants | 928 Participants | 230 Participants | 235 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 145 Participants | 141 Participants | 556 Participants | 128 Participants | 142 Participants |
| Sex: Female, Male Male | 93 Participants | 92 Participants | 388 Participants | 107 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 235 | 0 / 238 | 0 / 238 | 0 / 233 |
| other Total, other adverse events | 9 / 235 | 15 / 238 | 15 / 238 | 8 / 233 |
| serious Total, serious adverse events | 0 / 235 | 0 / 238 | 0 / 238 | 1 / 233 |
Outcome results
Primary
Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set
The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time frame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Population: Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set | -4.8213 Score on a scale | Standard Deviation 1.98247 |
| Group B: 1200 mg Acetylcysteine | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set | -4.7394 Score on a scale | Standard Deviation 1.9909 |
| Group C: 2400 mg Acetylcysteine | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set | -4.7758 Score on a scale | Standard Deviation 1.96938 |
| Group D: Placebo | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set | -5.0180 Score on a scale | Standard Deviation 1.98262 |
Primary
Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set
The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time frame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Population: Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set | -4.9085 Score on a scale | Standard Deviation 1.92431 |
| Group B: 1200 mg Acetylcysteine | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set | -4.8688 Score on a scale | Standard Deviation 1.84448 |
| Group C: 2400 mg Acetylcysteine | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set | -4.8002 Score on a scale | Standard Deviation 1.90569 |
| Group D: Placebo | Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set | -5.1256 Score on a scale | Standard Deviation 1.95072 |
Secondary
Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set
The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time frame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Population: Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 9 | 4.204 Score on a scale | Standard Deviation 2.8149 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 8 | 4.766 Score on a scale | Standard Deviation 2.8631 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 5 | 6.983 Score on a scale | Standard Deviation 2.7284 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 15 | 1.332 Score on a scale | Standard Deviation 2.1485 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 7 | 5.528 Score on a scale | Standard Deviation 2.9747 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 6 | 6.323 Score on a scale | Standard Deviation 2.7807 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 13 | 2.038 Score on a scale | Standard Deviation 2.4202 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 1 (Baseline) | 9.634 Score on a scale | Standard Deviation 1.1181 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 3 | 8.485 Score on a scale | Standard Deviation 2.3376 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 14 | 1.583 Score on a scale | Standard Deviation 2.3289 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 12 | 2.609 Score on a scale | Standard Deviation 2.52 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 11 | 3.051 Score on a scale | Standard Deviation 2.5229 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 4 | 7.821 Score on a scale | Standard Deviation 2.4482 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 2 | 9.021 Score on a scale | Standard Deviation 2.0348 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 10 | 3.634 Score on a scale | Standard Deviation 2.6815 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 12 | 2.754 Score on a scale | Standard Deviation 2.568 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 1 (Baseline) | 9.640 Score on a scale | Standard Deviation 1.0647 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 2 | 9.004 Score on a scale | Standard Deviation 1.9883 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 3 | 8.513 Score on a scale | Standard Deviation 2.2303 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 4 | 7.695 Score on a scale | Standard Deviation 2.513 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 5 | 6.979 Score on a scale | Standard Deviation 2.5706 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 6 | 6.203 Score on a scale | Standard Deviation 2.8719 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 7 | 5.538 Score on a scale | Standard Deviation 2.7449 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 8 | 4.750 Score on a scale | Standard Deviation 2.6755 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 9 | 4.322 Score on a scale | Standard Deviation 2.7254 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 10 | 3.763 Score on a scale | Standard Deviation 2.6391 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 11 | 3.284 Score on a scale | Standard Deviation 2.6658 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 13 | 2.246 Score on a scale | Standard Deviation 2.5296 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 14 | 1.941 Score on a scale | Standard Deviation 2.5375 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 15 | 1.614 Score on a scale | Standard Deviation 2.4459 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 4 | 7.723 Score on a scale | Standard Deviation 2.7156 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 12 | 2.756 Score on a scale | Standard Deviation 2.3795 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 14 | 1.836 Score on a scale | Standard Deviation 2.33 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 2 | 9.038 Score on a scale | Standard Deviation 2.1235 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 10 | 3.845 Score on a scale | Standard Deviation 2.6634 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 13 | 2.218 Score on a scale | Standard Deviation 2.4293 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 9 | 4.445 Score on a scale | Standard Deviation 2.7381 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 1 (Baseline) | 9.702 Score on a scale | Standard Deviation 1.0101 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 6 | 6.315 Score on a scale | Standard Deviation 2.798 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 11 | 3.256 Score on a scale | Standard Deviation 2.5716 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 5 | 7.013 Score on a scale | Standard Deviation 2.749 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 8 | 4.891 Score on a scale | Standard Deviation 2.7598 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 7 | 5.576 Score on a scale | Standard Deviation 2.8508 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 3 | 8.416 Score on a scale | Standard Deviation 2.439 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 15 | 1.634 Score on a scale | Standard Deviation 2.3178 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 4 | 7.761 Score on a scale | Standard Deviation 2.5058 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 8 | 4.387 Score on a scale | Standard Deviation 2.6004 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 10 | 3.404 Score on a scale | Standard Deviation 2.6805 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 9 | 3.839 Score on a scale | Standard Deviation 2.5924 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 14 | 1.596 Score on a scale | Standard Deviation 2.3637 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 3 | 8.609 Score on a scale | Standard Deviation 2.1298 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 11 | 2.843 Score on a scale | Standard Deviation 2.6469 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 2 | 9.074 Score on a scale | Standard Deviation 1.9866 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 12 | 2.413 Score on a scale | Standard Deviation 2.5608 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 15 | 1.352 Score on a scale | Standard Deviation 2.1882 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 5 | 6.917 Score on a scale | Standard Deviation 2.6312 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 13 | 1.943 Score on a scale | Standard Deviation 2.4174 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 6 | 6.039 Score on a scale | Standard Deviation 2.7838 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 1 (Baseline) | 9.683 Score on a scale | Standard Deviation 1.0652 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set | Day 7 | 5.126 Score on a scale | Standard Deviation 2.7096 |
Secondary
Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set
The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time frame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Population: Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 1 (Baseline) | 9.657 Score on a scale | Standard Deviation 1.1201 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 12 | 2.493 Score on a scale | Standard Deviation 2.3485 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 9 | 4.117 Score on a scale | Standard Deviation 2.7558 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 3 | 8.545 Score on a scale | Standard Deviation 2.289 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 10 | 3.521 Score on a scale | Standard Deviation 2.6127 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 11 | 2.934 Score on a scale | Standard Deviation 2.4039 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 4 | 7.803 Score on a scale | Standard Deviation 2.4779 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 2 | 9.080 Score on a scale | Standard Deviation 2.016 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 14 | 1.432 Score on a scale | Standard Deviation 2.0812 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 5 | 6.962 Score on a scale | Standard Deviation 2.7401 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 6 | 6.315 Score on a scale | Standard Deviation 2.7914 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 13 | 1.897 Score on a scale | Standard Deviation 2.2146 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 7 | 5.479 Score on a scale | Standard Deviation 2.955 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 15 | 1.221 Score on a scale | Standard Deviation 1.953 |
| Group A: 600 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 8 | 4.685 Score on a scale | Standard Deviation 2.825 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 8 | 4.605 Score on a scale | Standard Deviation 2.6399 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 12 | 2.572 Score on a scale | Standard Deviation 2.3785 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 5 | 6.874 Score on a scale | Standard Deviation 2.5865 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 9 | 4.181 Score on a scale | Standard Deviation 2.6773 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 2 | 8.935 Score on a scale | Standard Deviation 2.0268 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 11 | 3.144 Score on a scale | Standard Deviation 2.5214 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 13 | 2.065 Score on a scale | Standard Deviation 2.2949 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 10 | 3.628 Score on a scale | Standard Deviation 2.5174 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 3 | 8.395 Score on a scale | Standard Deviation 2.2583 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 7 | 5.400 Score on a scale | Standard Deviation 2.7151 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 15 | 1.409 Score on a scale | Standard Deviation 2.1312 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 14 | 1.749 Score on a scale | Standard Deviation 2.2779 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 6 | 6.093 Score on a scale | Standard Deviation 2.8809 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 4 | 7.577 Score on a scale | Standard Deviation 2.5472 |
| Group B: 1200 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 1 (Baseline) | 9.628 Score on a scale | Standard Deviation 1.0595 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 8 | 4.892 Score on a scale | Standard Deviation 2.7421 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 1 (Baseline) | 9.698 Score on a scale | Standard Deviation 1.0319 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 2 | 9.127 Score on a scale | Standard Deviation 2.0089 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 3 | 8.528 Score on a scale | Standard Deviation 2.2591 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 4 | 7.816 Score on a scale | Standard Deviation 2.5849 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 5 | 7.061 Score on a scale | Standard Deviation 2.6522 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 6 | 6.349 Score on a scale | Standard Deviation 2.7 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 7 | 5.604 Score on a scale | Standard Deviation 2.78 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 9 | 4.382 Score on a scale | Standard Deviation 2.6734 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 10 | 3.741 Score on a scale | Standard Deviation 2.5507 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 11 | 3.146 Score on a scale | Standard Deviation 2.4538 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 12 | 2.608 Score on a scale | Standard Deviation 2.2228 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 13 | 2.085 Score on a scale | Standard Deviation 2.2013 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 14 | 1.708 Score on a scale | Standard Deviation 2.1128 |
| Group C: 2400 mg Acetylcysteine | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 15 | 1.524 Score on a scale | Standard Deviation 2.0846 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 7 | 4.981 Score on a scale | Standard Deviation 2.7163 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 2 | 9.068 Score on a scale | Standard Deviation 2.0278 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 12 | 2.300 Score on a scale | Standard Deviation 2.4902 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 6 | 5.937 Score on a scale | Standard Deviation 2.8354 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 5 | 6.821 Score on a scale | Standard Deviation 2.6717 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 1 (Baseline) | 9.676 Score on a scale | Standard Deviation 1.0823 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 13 | 1.816 Score on a scale | Standard Deviation 2.3077 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 4 | 7.739 Score on a scale | Standard Deviation 2.575 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 3 | 8.594 Score on a scale | Standard Deviation 2.1921 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 15 | 1.193 Score on a scale | Standard Deviation 1.9636 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 10 | 3.222 Score on a scale | Standard Deviation 2.6197 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 9 | 3.652 Score on a scale | Standard Deviation 2.5495 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 14 | 1.444 Score on a scale | Standard Deviation 2.2198 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 11 | 2.705 Score on a scale | Standard Deviation 2.6042 |
| Group D: Placebo | Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set | Day 8 | 4.237 Score on a scale | Standard Deviation 2.5914 |
Secondary
Number of Responders and Non-responders to Treatment, Full Analysis Set
Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.
Time frame: Day 4, 7, 10 and 15
Population: Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Responders | 230 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Non-responders | 4 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Responders | 209 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Non-responders | 85 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Responders | 148 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Non-responders | 6 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Non-responders | 23 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Responders | 225 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Non-responders | 29 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Non-responders | 6 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Non-responders | 7 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Responders | 225 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Non-responders | 83 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Responders | 152 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Responders | 206 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Responders | 226 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Non-responders | 15 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Responders | 151 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Non-responders | 86 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Responders | 212 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Responders | 230 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Non-responders | 5 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Responders | 230 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Non-responders | 8 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Non-responders | 18 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 7 | Responders | 209 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Non-responders | 4 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 15 | Responders | 224 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Non-responders | 79 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Responders | 219 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 4 | Responders | 150 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Full Analysis Set | Day 10 | Non-responders | 6 Participants |
Secondary
Number of Responders and Non-responders to Treatment, Per-Protocol Set
Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.
Time frame: Day 4, 7, 10 and 15
Population: Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Responders | 138 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Non-responders | 75 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Responders | 192 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Non-responders | 21 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Responders | 207 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Non-responders | 6 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Responders | 211 Participants |
| Group A: 600 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Non-responders | 2 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Non-responders | 5 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Responders | 210 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Non-responders | 75 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Non-responders | 5 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Responders | 210 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Non-responders | 25 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Responders | 190 Participants |
| Group B: 1200 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Responders | 140 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Responders | 206 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Responders | 191 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Non-responders | 21 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Responders | 209 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Non-responders | 3 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Non-responders | 6 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Responders | 132 Participants |
| Group C: 2400 mg Acetylcysteine | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Non-responders | 80 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Responders | 192 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 7 | Non-responders | 15 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Non-responders | 73 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 4 | Responders | 134 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Responders | 202 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Non-responders | 2 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 15 | Responders | 205 Participants |
| Group D: Placebo | Number of Responders and Non-responders to Treatment, Per-Protocol Set | Day 10 | Non-responders | 5 Participants |
Secondary
Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set
SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome.
Time frame: Baseline (Day 1), Day 7 and Day 14
Population: Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 7 | -35.8 Score on a scale | Standard Deviation 33.25 |
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 14 | -79.3 Score on a scale | Standard Deviation 31.27 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 14 | -78.9 Score on a scale | Standard Deviation 31.11 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 7 | -38.2 Score on a scale | Standard Deviation 37.48 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 7 | -36.7 Score on a scale | Standard Deviation 34.61 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 14 | -78.6 Score on a scale | Standard Deviation 30.53 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 7 | -39.6 Score on a scale | Standard Deviation 30.42 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set | Day 14 | -81.5 Score on a scale | Standard Deviation 26.54 |
Secondary
Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set
SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome.
Time frame: Baseline (Day 1), Day 7 and Day 14
Population: Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 7 | -36.4 Score on a scale | Standard Deviation 32.64 |
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 14 | -79.8 Score on a scale | Standard Deviation 30.9 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 14 | -78.6 Score on a scale | Standard Deviation 31.77 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 7 | -39.5 Score on a scale | Standard Deviation 36.68 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 7 | -36.7 Score on a scale | Standard Deviation 33.44 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 14 | -79.1 Score on a scale | Standard Deviation 30.16 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 7 | -39.6 Score on a scale | Standard Deviation 30.6 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set | Day 14 | -81.0 Score on a scale | Standard Deviation 27.1 |
Secondary
Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set
SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL.
Time frame: Baseline (Day 1), Day 7 and Day 14
Population: Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 1 (Baseline) | 37.8 Score on a scale | Standard Deviation 16.89 |
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 14 | 7.2 Score on a scale | Standard Deviation 10.8 |
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 7 | 23.6 Score on a scale | Standard Deviation 15.01 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 1 (Baseline) | 36.3 Score on a scale | Standard Deviation 15.82 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 14 | 6.9 Score on a scale | Standard Deviation 11.15 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 7 | 21.2 Score on a scale | Standard Deviation 13.14 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 7 | 22.3 Score on a scale | Standard Deviation 13.95 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 1 (Baseline) | 36.7 Score on a scale | Standard Deviation 16.21 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 14 | 7.0 Score on a scale | Standard Deviation 10.07 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 1 (Baseline) | 36.3 Score on a scale | Standard Deviation 17 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 14 | 6.5 Score on a scale | Standard Deviation 10.28 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set | Day 7 | 21.1 Score on a scale | Standard Deviation 13.56 |
Secondary
Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set
SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL.
Time frame: Baseline (Day 1), Day 7 and Day 14
Population: Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 1 (Baseline) | 37.7 Score on a scale | Standard Deviation 16.64 |
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 14 | 6.9 Score on a scale | Standard Deviation 10.49 |
| Group A: 600 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 7 | 23.3 Score on a scale | Standard Deviation 14.92 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 1 (Baseline) | 36.7 Score on a scale | Standard Deviation 15.89 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 14 | 7.1 Score on a scale | Standard Deviation 11.43 |
| Group B: 1200 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 7 | 21.2 Score on a scale | Standard Deviation 13.32 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 7 | 22.2 Score on a scale | Standard Deviation 14.27 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 1 (Baseline) | 36.4 Score on a scale | Standard Deviation 15.86 |
| Group C: 2400 mg Acetylcysteine | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 14 | 6.8 Score on a scale | Standard Deviation 9.67 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 1 (Baseline) | 36.2 Score on a scale | Standard Deviation 16.88 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 14 | 6.6 Score on a scale | Standard Deviation 10.5 |
| Group D: Placebo | Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set | Day 7 | 21.0 Score on a scale | Standard Deviation 13.78 |
Secondary
Time to Onset of Action, Full Analysis Set
Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value\<0.05) improvement from placebo.
Time frame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Population: Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: 600 mg Acetylcysteine | Time to Onset of Action, Full Analysis Set | NA Days |
| Group B: 1200 mg Acetylcysteine | Time to Onset of Action, Full Analysis Set | NA Days |
| Group C: 2400 mg Acetylcysteine | Time to Onset of Action, Full Analysis Set | NA Days |
Secondary
Time to Onset of Action, Per-Protocol Set
Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value\<0.05) improvement from placebo.
Time frame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Population: Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: 600 mg Acetylcysteine | Time to Onset of Action, Per-Protocol Set | NA Days |
| Group B: 1200 mg Acetylcysteine | Time to Onset of Action, Per-Protocol Set | NA Days |
| Group C: 2400 mg Acetylcysteine | Time to Onset of Action, Per-Protocol Set | NA Days |