Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis

NCT04123405 | Completed Phase 3 Results

• 2 other identifiers: 2018-08-EFT-12019-000060-20
• Study Type: interventional
• Target: 944
• Locations: 4 countries
• Sites: 37

Brief Summary

The trial was conducted as a prospective, randomized, multinational, multicenter, double-blind study in 4 parallel groups of patients.

Conditions

Rhinosinusitis

Keywords

acute uncomplicated rhinosinusitis, acetylcysteine

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

• 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.

  Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Secondary Outcomes (10)

• 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, Per-Protocol Set

  Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

• 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

• 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

• Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set

  Baseline (Day 1), Day 7 and Day 14

Study Arms (4)

Group A: 600 mg acetylcysteine

EXPERIMENTAL

one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)

Drug: acetylcysteine; Drug: Placebo

Group B: 1200 mg acetylcysteine

EXPERIMENTAL

two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)

Drug: acetylcysteine; Drug: Placebo

Group C: 2400 mg acetylcysteine

EXPERIMENTAL

four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)

Drug: acetylcysteine

Group D: Placebo

PLACEBO COMPARATOR

four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)

Drug: Placebo

Interventions

acetylcysteine DRUG

600 mg tablet

Group A: 600 mg acetylcysteine; Group B: 1200 mg acetylcysteine; Group C: 2400 mg acetylcysteine

Placebo DRUG

Placebo to acetylcysteine

Group A: 600 mg acetylcysteine; Group B: 1200 mg acetylcysteine; Group D: Placebo

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged between 14 and 75 years inclusive on the date of consent
• Diagnosis of acute, uncomplicated rhinosinusitis defined at screening visit 1 and at Visit 2 as:
• 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
• individual score for facial pain/pressure ≥1 (mild) and ≤2 (moderate)
• presence of symptoms ≤3 days prior to screening visit
• 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.

You may not qualify if:

• History of hypersensitivity or intolerance to the active substance or any of the excipients of the trial medication
• Patient with history of hereditary fructose intolerance, galactose intolerance, lactase deficiency or glucose-galactose malabsorption
• Chronic rhinosinusitis (symptoms lasting longer than 3 months)
• Subjects who have undergone sinus or nasal surgery for chronic rhinosinusitis in the 6 months prior to screening visit
• Sinus lavage within 7 days prior to screening visit
• Odontogenic rhinosinusitis
• Allergic (perennial or seasonal) rhinitis
• Bronchial asthma or chronic obstructive pulmonary disease
• Nasal polyposis or clinically relevant nasal septum deviation
• Concomitant otitis
• Intranasal or systemic use of corticosteroids within 30 days prior to screening visit
• Intranasal or systemic use of antibiotics within 30 days prior to screening visit
• Use of nasal decongestants within 2 days prior to screening visit
• Concomitant treatment of common cold-like symptoms within 7 days prior to screening visit with any of the following:
• Analgesics

Sponsors & Collaborators

• Sandoz: lead

Study Sites (37)

Sandoz Investigative Site

Burgas, 8000, Bulgaria

Location

Sandoz Investigative Site

Gabrovo, 5300, Bulgaria

Location

Sandoz Investigative Site

Plovdiv, 4000, Bulgaria

Location

Sandoz Investigative Site

Sliven, 8800, Bulgaria

Location

Sandoz Investigative Site

Sofia, 1000, Bulgaria

Location

Sandoz Investigative Site

Sofia, 1408, Bulgaria

Location

Sandoz Investigative Site

Sofia, 1527, Bulgaria

Location

Sandoz Investigative Site

Sofia, 1606, Bulgaria

Location

Sandoz Investigative Site

Yambol, 8600, Bulgaria

Location

Sandoz Investigative Site

Aachen, 52074, Germany

Location

Sandoz Investigative Site

Dresden, 01139, Germany

Location

Sandoz Investigative Site

Duisburg, 47051, Germany

Location

Sandoz Investigative Site

Chisinau, 2012, Moldova

Location

Sandoz Investigative Site

Chisinau, 2025, Moldova

Location

Sandoz Investigative Site

Chisinau, 2032, Moldova

Location

Sandoz Investigative Site

Chisinau, 2044, Moldova

Location

Sandoz Investigative Site

Chisinau, 2051, Moldova

Location

Sandoz Investigative Site

Chisinau, 37, Moldova

Location

Sandoz Investigative Site

Orhei, 3005, Moldova

Location

Sandoz Investigative Site

Kazan', 420029, Russia

Location

Sandoz Investigative Site

Kemerovo, 650066, Russia

Location

Sandoz Investigative Site

Moscow, 117552, Russia

Location

Sandoz Investigative Site

Moscow, 119571, Russia

Location

Sandoz Investigative Site

Moscow, 123184, Russia

Location

Sandoz Investigative Site

Moscow, 142190, Russia

Location

Sandoz Investigative Site

Novosibirsk, 630051, Russia

Location

Sandoz Investigative Site

Ryazan, 390026, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 191025, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 191186, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 192283, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 194291, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 195197, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 196084, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 196158, Russia

Location

Sandoz Investigative Site

Saint Petersburg, 197376, Russia

Location

Sandoz Investigative Site

Smolensk, 214031, Russia

Location

Sandoz Investigative Site

Yaroslavl, 150000, Russia

Location

MeSH Terms

Conditions

Rhinosinusitis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Rhinitis; Respiratory Tract Infections; Infections; Sinusitis; Paranasal Sinus Diseases; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Sandoz

  Sandoz

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 10, 2019
• Study Start: October 22, 2020
• Primary Completion: April 20, 2021
• Study Completion: April 20, 2021
• Last Updated: November 19, 2021
• Results First Posted: November 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

MO (7); DE (3); RU (18); BU (9)