Regulatory Decision Summary for Quinsair

Health Canada considers that the benefits of Quinsair in managing chronic pulmonary Pseudomonas aeruginosa (P. aeruginosa) infections in patients ≥18 years of age with cystic fibrosis (CF) outweigh the potential risks.

Benefits

Clinical efficacy of Quinsair, a solution for inhalation, was evaluated in an open-label, active-comparator study (Study 209 Core Phase, 3 treatment cycles, active-comparator was tobramycin inhalation solution) with an optional open-label uncontrolled extension (Study 209 Extension Phase, up to 3 additional cycles) and from two double-blind, single-cycle, placebo-controlled trials (Studies 204 and 207).

There is evidence that Quinsair 240 mg twice daily (BID) offers some benefit to the patients who have used tobramycin inhalation solution for at least 3 cycles in the prior year and were tolerant of the therapy. Overall, Quinsair was associated with improvements in pulmonary function from baseline across efficacy studies. In the active-controlled Study 209, the mean change from baseline in percent predicted Forced Expiratory Volume in 1 second (FEV₁) was numerically greater with Quinsair 240 mg BID than with tobramycin inhalation solution 300 mg BID over 1 to 3 cycles (each cycle corresponding to 28 days on and 28 days off study treatment) and non-inferiority of Quinsair to tobramycin inhalation solution was met against the pre-defined margin (4%). The study showed that the actual changes from baseline to Day 28 in percent predicted FEV₁ were modest but were at least as good as and numerically better for Quinsair. The two placebo-controlled studies showed that 28 days treatment with Quinsair 240 mg BID resulted in significant improvement in relative change from baseline in percent predicted FEV₁ compared to placebo. In addition, in the extension study, when patients receiving tobramycin inhalation solution were switched to Quinsair, a benefit in FEV₁ was observed. Although the numbers were small, the results seem to support the value of alternating different inhaled antibiotic agents in a rotational manner.

Risks

Quinsair was generally well tolerated during the clinical study program. There were no deaths in the CF clinical program. The most frequently reported adverse reactions (considered related to Quinsair by the Study Investigator) were dysgeusia (31%), cough/productive cough (10%) and increased sputum (5%). Overall, the results suggest that Quinsair is an irritant to the upper and lower airways.

Multiple dose administration of Quinsair 240 mg BID resulted in levofloxacin systemic exposure approximately 50% lower than that observed following systemic administration of 500 mg levofloxacin or approximately equal to that observed following oral administration of 250 mg levofloxacin (lowest recommended dose). Therefore, adverse events which are known to be associated with systemic administration of levofloxacin or the fluoroquinolone class may occur in patients receiving Quinsair. The safety concerns from systemically administered levofloxacin or the fluoroquinolone class have been included in the Quinsair Product Monograph.