Little more than two weeks after commencing a European phase III trial of AM-101 in patients with acute peripheral tinnitus, Auris Medical AG has now begun a North American phase III study of the drug. Results from the two trials are expected next year, and, if positive, they could form the basis of regulatory submissions on either side of the Atlantic during the first quarter of 2016.

The North American study has already recruited the first of 330 patients with acute tinnitus in the inner ear due to trauma to the cochlea or due to otitis media (an infection of the middle ear). The double-blind, placebo-controlled trial is limiting enrollment to patients within three months of onset.

The European study is recruiting almost twice that figure – 600 patients in all – as it will examine the drug’s safety and efficacy in both the acute setting and the post-acute setting, defined as between four and 12 months after the onset of tinnitus. Patients will receive a single cycle of treatment, which comprises three intratympanic injections administered over a period between three and five days.

The primary endpoint on the European study is based on a patient-reported outcome, an improvement from baseline in a 10-point numerical scale of tinnitus loudness.

“We agreed with the EMA on a responder definition – a two-point improvement,” Thomas Meyer, founder and CEO of Basel, Switzerland-based Auris, told BioWorld Today. In the U.S., it has agreed with the FDA, under a special protocol assessment, to use two co-primary endpoints, an improvement on the tinnitus loudness scale and patient responses to a questionnaire called the Tinnitus Functional Index.

Data from the two studies will support filings in each jurisdiction. “They’re really mirror-like,” Meyer said. “Just to compensate for this co-primary [endpoint] we’ve increased the size of the N by 10 percent for this U.S. trial.”

The post-acute arm of the European trial will also enable the company to explore the drug’s efficacy beyond the arbitrary three-month cut-off point.

A multiple regression analysis on phase II data indicated that the “age” of tinnitus did not appear to affect the drug’s impact. Patients who complete either study will be able to enroll onto an open-label safety study, involving up to three further AM-101 treatment cycles, administered over nine months.

AM-101 is an N-methyl-D-aspartate receptor (NMDA) antagonist. It is thought to act in tinnitus by damping down a glutamate-triggered, phantom excitation of the auditory nerve, which arises from damage to the cochlea, the spiral-shaped, fluid-filled cavity in the inner ear where sound vibrations are transduced into nerve signals.

Although millions of people suffer from tinnitus, of varying duration and due to various causes, Auris is focused on a defined patient population whose condition is due to a recent and identifiable cause, such as exposure to very loud music. Should this strategy be successful, it will then explore further opportunities to broaden the label.

The company is keeping its commercialization options open for now.

It is tempted, Meyer said, to commercialize the drug itself, with a goal of becoming the ‘Alcon’ of otology. Diagnosis of the problem is not complicated; patients are aware of their condition; and the main clinical audience in the U.S. is the 9,000 ear, nose and throat specialists who can administer intratympanic injections. The company is not locked into any strategy for now, however.