3児の親さん薬剤師のブログ

とある薬剤師です。感染症治療を考える素材をちょこっと提供。https://note.mu/twin1980。

Efficacy and Safety of IV-to-Oral Lefamulin, a Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial Pneumonia: The Phase 3 LEAP 1 Trial

CIDから報告された、LEAP

CAPに対する Lefamulin vs  moxifloxacin の P3 RCT。

 

非劣勢マージン12.5と10%

 

The US FDA primary endpoint was early clinical response (ECR) 96±24 hours after the first dose of study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%).

The EMA co-primary endpoints were investigator assessment of clinical response (IACR) 5-10 days after last dose of study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%).

 

academic.oup.com

f:id:akinohanayuki:20190206054312j:plain

 

感想

 

CAPに対して、Lefamulinは、moxifloxacinに非劣勢であった。 

新薬なため、未知の副作用や耐性化しやすさなども慎重にウォッチ必要ですね。

 

 

Abstract


Background

Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study (NCT02559310) was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP.

Methods

In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin 150 mg intravenously (IV) q12h or moxifloxacin 400 mg IV q24h. After 6 doses, patients could be switched to oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US FDA primary endpoint was early clinical response (ECR) 96±24 hours after the first dose of study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The EMA co-primary endpoints were investigator assessment of clinical response (IACR) 5-10 days after last dose of study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%).

Results

551 patients were randomized (n=276 lefamulin; n=275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%; difference: –2.9% [95% confidence interval: –8.5, 2.8]) and IACR (mITT, 81.7% vs 84.2%; difference –2.6% [–8.9, 3.9]; CE, 86.9% vs 89.4%; difference –2.5% [–8.4, 3.4]). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin.

Conclusions

Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated.

 

Lefamulinとは?

 

Lefamulin is a semi-synthetic pleuromutilin antibiotic with potential to be first-in-class for systemic administration in humans discovered and developed by the Nabriva Therapeutics team.

It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. Lefamulin’s binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes.

 

investors.nabriva.com