Aradigm reported that the final patient has completed the last dose appointment in the ORBIT-3 and ORBIT-4 Phase 3 clinical trials assessing Pulmaquin for the treatment of non-cystic fibrosis bronchiectasis (non-CF BE) in patients with chronic infection by Pseudomonas aeruginosa bacteria.
Pulmaquin is a dual release formulation drug combining liposome encapsulated and unencapsulated ciprofloxacin, an agent widely used to treat acute and chronic lung infections and that has a broad spectrum of antibacterial activity.
The Phase 3 clinical program of Pulmaquin in non-CF BE patients was designed to determine the safety and effectiveness of the drug as a once-daily inhaled formulation. The two global, double-blind, placebo-controlled pivotal clinical trials ORBIT-3 and ORBIT-4 had a similar design with the exception of a pharmacokinetics sub-study that was conducted in one of the trials.
ORBIT-3 included 278 patients and ORBIT-4 included 304 patients who took part in a 48-week experiment involving treatment with either Pulmaquin or a placebo. Patients received treatment every 28 days for six cycles, and had 28 days off the treatment, which was followed by a 28-day open label extension period in which all patients received Pulmaquin.
The primary endpoint of the trials is the time to first pulmonary exacerbation, and secondary endpoints are a reduction in pulmonary exacerbations and quality of life improvement. Monitoring patients’ lung function determined the drug’s safety profile.
In a press release, Dr. Juergen Froehlich, MD, chief medical officer of Aradigm, a specialty pharmaceutical company, thanked the patients with non-CF BE “for their dedication and successful participation” who took part in the clinicial trials.
“We are now focusing on expeditiously closing out both trials with data from a total of 582 enrolled subjects. We anticipate that the top line data will be available in the fourth quarter of this year,” Froehlich said.
Pulmaquin’s effectiveness has previously been studied in preclinical safety trials, as well as in Phase 1 and 2 studies. In the phase 2b study called ORBIT-2, researchers were able to demonstrate the ability of Pulmaquin in reducing the activity of the bacteria P. aeruginosa, as well as the time for the first exacerbation, in 42 adult patients with non-CF BE.
“Both trials [ORBIT-3 and ORBIT-4] were designed to confirm the encouraging clinical data from the earlier Phase 2b ORBIT-2 clinical trial that demonstrated a substantial antimicrobial effect combined with an extension of the exacerbation free interval in subjects treated with Pulmaquin as compared to placebo,” Froehlich said.
Aradigm has been granted orphan drug designation for liposomal ciprofloxacin and ciprofloxacin for inhalation for non-CF BE in the U.S. Pulmaquin has also been designated as a Qualified Infectious Disease Product (QIDP) by the U.S. Food and Drug Administration (FDA) for the treatment of non-CF BE patients with chronic P. aeruginosa lung infections, which made the drug eligible for Fast-Track designation by the FDA, granted in 2014.
Non-CF BE is a severe, chronic and rare disease, frequently associated with chronic lung infections and characterized by an abnormal dilatation of the bronchi and bronchioles. The condition has a high morbidity and mortality, affecting more than 110,000 individuals in the U.S. and more than 200,000 people in Europe. There is no approved drug treatment for this disease.