Mixed Results Reported for Inhaled Antibiotic in Late-Stage Trials

Ciprofloxacin formulation studied in lung infections

Pulmaquin (Aradigm Corporation), a once-daily inhaled formulation of ciprofloxacin, has failed to meet the primary endpoint in a late-stage study involving patients with non-cystic fibrosis bronchiectasis (non-CF BE) who had chronic lung infections with Pseudomonas aeruginosa. In another study, however, Pulmaquin was deemed to have had a statistically significant benefit over placebo.

Pulmaquin is a dual-release formulation composed of a mixture of liposome-encapsulated and unencapsulated ciprofloxacin. Ciprofloxacin, available in oral and intravenous formulations, is widely used to treat acute lung infections and is often preferred because of its broad-spectrum antibacterial activity against various bacteria, such as P. aeruginosa.

The ORBIT-3 and ORBIT-4 pivotal trials were identical in design except for a pharmacokinetics substudy that was conducted in one of the studies. The primary endpoint in both trials was an increase in the median time to the first mild, moderate, or severe pulmonary exacerbation (PE). The key secondary efficacy endpoint in both studies was the frequency of PEs during the 48-week, double-blind treatment period.

In the ORBIT-3 trial, the median time to the first mild, moderate, or severe PE was 221 days in the Pulmaquin group compared with 136 days in the placebo group. This increase in the median time to the first PE was not statistically significant (P = 0.8488). In the key secondary efficacy endpoint, there was a 13% reduction in the frequency of PEs during the 48-week treatment period in the Pulmaquin group compared with the placebo group. This result also was not statistically significant (P = 0.3125).

In the ORBIT-4 trial, the median time to the first mild, moderate, or severe PE was 230 days in the Pulmaquin group compared with 163 days in the placebo group (P = 0.0462). In the key secondary efficacy endpoint, there was a 37% reduction in the frequency of PEs during the 48-week treatment period in the Pulmaquin group compared with the placebo group (P = 0.0007).

Overall, the incidence of treatment-emergent adverse events (TEAEs) was similar between the Pulmaquin and placebo groups in both the ORBIT-3 trial (Pulmaquin, 90%; placebo, 92%) and the ORBIT-4 trial (Pulmaquin: 86%; placebo: 97%). In ORBIT-3, the rates of serious TEAEs were 31% for Pulmaquin and 25% for placebo, whereas in ORBIT-4, the rates were 17% and 29%, respectively.

The FDA has granted an orphan drug designation to Pulmaquin for the treatment of patients with non-CF BE.

Sources: Aradigm Corporation; December 1, 2016; and Reuters; December 1, 2016.