BRONCHITOL® (mannitol) inhalation powder improves FEV1

Across three 26-week clinical trials, BRONCHITOL led to a sustained improvement in FEV1 vs control1,2

  • In Trial 1, mean percent predicted FEV1 was 63.9% (range: 40.3%–89.6%)1
  • In all three trials, improvement in FEV1 was significant with or without concomitant rhDNase with BRONCHITOL vs control*†2

Study Design: All three trials were 26-week, randomized, double-blind, controlled studies in patients with CF. Patients were randomized to receive either BRONCHITOL 400 mg or control (50 mg inhaled mannitol) twice daily. Results from Trials 2 and 3 were based on a post-hoc analysis that included adult patients (≥18 years old). Of the 761 adult patients, 45% of patients were female and 98% were Caucasian; 414 received BRONCHITOL and 347 received control for up to 26 weeks. Adult patients treated with BRONCHITOL were ages 18 to 59 years with a baseline ppFEV1 of 62.0%. The primary efficacy endpoint was improvement in lung function measured by the mean change from baseline in pre-dose FEV1 (mL) over 26 weeks of treatment. The use of inhaled hypertonic saline was not permitted, but continued use of other standard of care CF therapies was allowed (e.g., bronchodilators, inhaled antibiotics, and rhDNase).

Results based on stratified analyses using integrated data from phase 3 trials for the change from baseline in FEV1 over the 26-week treatment period
(ITT population). Subgroup demographics were not balanced, and the study was not powered to evaluate the respective subgroup outcomes, therefore
results should be interpreted with caution.

Among patients receiving treatment with rhDNase during the study period (64.4% of the overall population), the adjusted mean difference from baseline
in FEV1 between the BRONCHITOL and control groups was 0.048 L (95% CI: 0.009, 0.086), P=0.015. Among patients not receiving rhDNase (35.6% of
the overall population), the adjusted mean difference from baseline in FEV1 between groups was 0.100 L (95% CI: 0.044, 0.156), P<0.001.

Significantly greater sputum weight was observed in patients treated with BRONCHITOL vs control3

Trial 2 and Trial 3: Post-Treatment Sputum Weight In Adults

Sputum was collected during and for 30 minutes following the initial dose of study medication and then weighed. Data are available from Trials 2 and 3.

Sputum weight differences were assessed as part of a post-hoc analysis based on pooled data from two multicenter, randomized, double-blind, controlled, parallel group Phase 3 studies in which adult patients (≥18 years old) received either BRONCHITOL 400 mg or control (50 mg inhaled mannitol) twice a day for 26 weeks (n=341). Adult treatment and control groups were well matched at baseline for age, BMI, gender, FEV1, concurrent rhDNase use, nebulized antibiotic use, and P. aeruginosa. Sputum was collected during and for 30 minutes after the initial dose of medication and then weighed to evaluate any differences. No conclusion of efficacy can be drawn from these data specific to sputum weight.

Trial 2: Primary endpoint of this study was FEV1 change from baseline (mL), while secondary endpoints included pulmonary exacerbations, quality of life scores using the Cystic Fibrosis Questionnaire-R (CFQ-R), rescue antibiotic use (number of agents, course, and days of use), change in absolute FVC, FEF25-75 from baseline, and days in hospital due to pulmonary exacerbations. Safety endpoints included adverse events, laboratory safety tests including complete blood count, urea and electrolytes, and liver function tests, qualitative sputum microbiology, bronchodilator response before and after treatment, and physical examination.

Trial 3: Primary endpoint of this study was change in absolute FEV1 from baseline (mL), while secondary endpoints included pulmonary exacerbations, quality of life scores using the CFQ-R, rescue antibiotic use (number of agents, course, and days of use), change in absolute FVC, FEF25-75 from baseline, and days in hospital due to pulmonary exacerbations. Safety endpoints included adverse events, hematology and biochemistry, vital signs and physical examination, and qualitative sputum microbiology as well as quantitative sputum microbiology for S. aureus and P. aeruginosa.

BRONCHITOL Blister Pack and Inhaler

BRONCHITOL dosing and administration

BRONCHITOL is not intended to be used as a rescue medication. Inhaler and blister pack are not actual size and are for representation only. Use an inhaled bronchodilator 5–15 minutes before taking BRONCHITOL.

Important Safety
Information

BRONCHITOL is contraindicated in patients with hypersensitivity to mannitol or to any of the capsule components. BRONCHITOL is contraindicated in patients who fail to pass the BRONCHITOL Tolerance Test (BTT).

BRONCHITOL can cause bronchospasm, which can be severe in susceptible patients. Because of the risk of bronchospasm, prior to prescribing BRONCHITOL, patients must pass the BRONCHITOL Tolerance Test (BTT). The BTT must be administered under the supervision of a healthcare practitioner who can treat severe bronchospasm.

Patients who pass the BRONCHITOL tolerance test (BTT) may experience bronchospasm with add-on maintenance therapy with BRONCHITOL. Patients should premedicate with an inhaled short-acting bronchodilator prior to each administration of BRONCHITOL. If bronchospasm occurs, immediately discontinue BRONCHITOL and treat bronchospasm with an inhaled short-acting bronchodilator.

Hemoptysis can occur with BRONCHITOL use. Monitor patients with history of episodes of hemoptysis. If hemoptysis occurs, discontinue use of BRONCHITOL.

Most common adverse reactions (≥3%) include cough, hemoptysis, oropharyngeal pain, vomiting, bacteria sputum identified, pyrexia, and arthralgia.

Please see Full Prescribing Information.

Indication

BRONCHITOL® (mannitol) inhalation powder is a sugar alcohol indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years of age and older with cystic fibrosis. Use BRONCHITOL only in adults who have passed the BRONCHITOL Tolerance Test.

Please see Full Prescribing Information.

References: 1. BRONCHITOL® (mannitol) inhalation powder Prescribing Information. 2020. 2. Data on file. Chiesi USA, Inc. 3. Aitken ML, Bilton D, Fox H, Charlton B; CF-301 and CF-302 Study Investigators. Bronchitol (inhaled dry powder mannitol) in adult patients with cystic fibrosis [abstract 47]. J Cyst Fibros. 2012;11(suppl1):S68.