Adult Patients

A total of 1231 adults with a diagnosis of CABP were enrolled in two randomized, multi-center, multinational, double-blind, non-inferiority trials (Trials 1 and 2) comparing Teflaro (600 mg administered IV over 1 hour every 12 hours) with ceftriaxone (1 g ceftriaxone administered IV over 30 minutes every 24 hours). In both treatment groups of CABP Trial 1, two doses of oral clarithromycin (500 mg every 12 hours), were administered as adjunctive therapy starting on Study Day 1. No adjunctive macrolide therapy was used in CABP Trial 2. Patients with known or suspected MRSA were excluded from both trials. Patients with new or progressive pulmonary infiltrate(s) on chest radiography and signs and symptoms consistent with CABP with the need for hospitalization and IV therapy were enrolled in the trials. Treatment duration was 5 to 7 days. A switch to oral therapy was not allowed. Among all subjects who received any amount of study drug in the two CABP trials, the 30-day all-cause mortality rates were 11/609 (1.8%) for the Teflaro group vs. 12/610 (2.0%) for the ceftriaxone group, and the difference in mortality rates was not statistically significant.

To evaluate the treatment effect of ceftaroline, an analysis was conducted in CABP patients for whom the treatment effect of antibacterials may be supported by historical evidence. The analysis endpoint required subjects to meet sign and symptom criteria at Day 4 of therapy: a responder had to both (a) be in stable condition, based on temperature, heart rate, respiratory rate, blood pressure, oxygen saturation, and mental status; (b) show improvement from baseline on at least one symptom of cough, dyspnea, pleuritic chest pain, or sputum production, while not worsening on any of these four symptoms. The analysis used a microbiological intent-to-treat population (mITT population) containing only subjects with a confirmed bacterial pathogen at baseline. Results for this analysis are presented in Table 12.

The protocol-specified analyses included clinical cure rates at the TOC (8 to 15 days after the end of therapy) in the co-primary Modified Intent-to-Treat Efficacy (MITTE) and CE populations (Table 13) and clinical cure rates at TOC by pathogen in the Microbiologically Evaluable (ME) population (Table 14). However, there are insufficient historical data to establish the magnitude of drug effect for antibacterials drugs compared with placebo at a TOC time point. Therefore, comparisons of Teflaro to ceftriaxone based on clinical response rates at TOC cannot be utilized to establish non-inferiority. Neither trial established that Teflaro was statistically superior to ceftriaxone in terms of clinical response rates. The MITTE population included all patients who received any amount of study drug according to their randomized treatment group and were in PORT (Pneumonia Outcomes Research Team) Risk Class III or IV. The CE population included patients in the MITTE population who demonstrated sufficient adherence to the protocol.

Pediatric Patients

The CABP pediatric trial was a randomized, parallel-group, active controlled trial in pediatric patients 2 months to < 18 years of age. 

A total of 161 children with a diagnosis of CABP were enrolled in a randomized, multi-center, multinational, active controlled trial comparing Teflaro with ceftriaxone. Patients with new or progressive pulmonary infiltrate(s) on chest radiography and signs and symptoms consistent with CABP including acute onset or worsening symptoms of cough, tachypnea, sputum production, grunting, chest pain, cyanosis, or increased work of breathing with the need for hospitalization and IV therapy were enrolled in the trial. Treatment duration was 5 to 14 days. A switch to oral therapy with amoxicillin clavulanate was allowed on Study Day 4.

The primary objective was to evaluate the safety and tolerability of Teflaro. The study was not powered for comparative inferential efficacy analysis, and no efficacy endpoint was identified as primary.

To evaluate the treatment effect of Teflaro, an analysis was conducted in 143 patients with CABP in the MITT population. This analysis evaluated responder rates at Study Day 4 based on achieving improvement in at least 2 out of 7 symptoms (cough, dyspnea, chest pain, sputum production, chills, feeling of warmth / feverish and exercise intolerance or lethargy) and have worsening in none of these symptoms. 

The clinical response at Study Day 4 was 69.2% (74/107) for Teflaro and 66.7% (24/36) for the comparator, with a treatment difference of 2.5% (95% CI of –13.9, 20.9).

Clinical cure rates at test of cure were 87.9% (94/107) for Teflaro and 88.9% (32/36) for the comparator, with a treatment difference of -1.0 (95% CI –11.5, 14.1).