Cempra, Inc., a clinical-stage pharmaceutical company, has initiated global phase III clinical trial of orally-administered solithromycin, the company's fluoroketolide antibiotic candidate, in patients with community-acquired bacterial pneumonia (CABP).
The phase III study is a double-blind, placebo-controlled and global multi-center study in which approximately 800 patients with PORT-II to PORT-IV CABP will be randomized to receive either oral solithromycin, an 800 mg loading dose followed by 400 mg once daily for a total of five days, or once-daily oral administration of 400 mg of moxifloxicin for seven days. The primary endpoint will be non-inferiority of early response at 72 hours, which is specified by the proposed FDA guidance.
"Physicians need safe, convenient and active antibiotics to treat CABP, a disease that is the number one cause of death due to infection," said Prabhavathi Fernandes, Ph.D., president and chief executive officer of Cempra. "Current therapy for moderate to moderately-severe CABP is a choice between combination therapy with intravenous antibiotics or oral administration of fluoroquinolone antibiotics. The former involves intravenous therapy, possibly requiring hospital admission and the latter has been associated with significant side effects, possibly including Clostridium difficile infection due to the class's broad activity spectrum.
"Solithromycin's profile is emerging as a truly differentiated molecule. The drug has shown a favorable safety profile in over 400 patients including when compared to levofloxacin in a phase II trial in CABP patients. The compound may offer both flexibility and convenience as it is in development for both oral and intravenous formulations. The drug may provide the option of IV-to-oral step down monotherapy to send patients home from the hospital sooner. In addition, and as this clinical trial may demonstrate, patients may be able to avoid hospital admission by starting on the oral form as monotherapy. We expect to complete the trial in the first half of 2014."
Solithromycin is the first fluoroketolide with a number of attributes that may provide clinically important advantages over several comparator products:
Eight to 16 times more potent than azithromycin and is active against organisms that have become resistant to azithromycin.
Potent in vitro activity against a broad range of respiratory pathogens, including pneumococci, beta-hemolytic streptococci, staphylococci, haemophilus, legionella, mycoplasma, moraxella and chlamydophila.
Potent in vitro activity against other medically significant pathogens, including CA-MRSA, M. avium, malaria, enterococci and gonococci.
Good tolerability to date as demonstrated in phase I and II trials of the oral formulation.
Low resistance frequency in vitro.
No pyridine sidechain, unlike telithromycin; the pyridine moiety is believed responsible for certain adverse effects observed with telithromycin (Ketek).
Excellent tissue distribution and intracellular tissue concentrations, including lung epithelial lining fluid and alveolar macrophages.
Oral and IV formulations concurrently in development.