The results of the Phase 2b safety and efficacy trial of intratympanic sustained release dexamethasone for Meniere's disease was just published. This was a randomized, double-blind, placebo controlled study of 154 adult patients. The results did not meet all predefined endpoints, but it did demonstrate reductions in various vertigo outcome measures.
The protocol involved injecting either 12 milligrams of dexamethasone or a placebo into the middle ear of patients with the diagnosis of definitive unilateral Meniere's disease by AAO-HNS criteria. The active drug is known as OTO-104. It is a thermosensitive polymer that is a liquid at room temperature, but quickly becomes a gel at body temperature after intratympanic injection. It has mucoadhesive properties and thus maintains its position near the round window after injection. The steroid micro particles are designed to provide a sustained exposure of the steroid to the inner ear over a 7 week period. After the injection, the placebo and the active groups were followed monthly for 4 months.
To qualify for the study, patients underwent a one month lead in phase during which time they documented their vertigo attacks. To be included in the study, at least 2 days of definitive vertigo episodes were required. Outcome measures included a change in vertigo frequency at month 3 compared to the one month lead in period; the number of monthly definitive vertigo days; the vertigo severity score (from 1-5) for each episode; and the daily vertigo count measured for each month after the injection.
The results showed a reduction in days of the vertigo from 8 during the lead in month to 3 at the end of month 3. This change, however, did not reach statistical significance (p value = 0.067). The number of vertigo days, however, did significantly decrease at month 2 and 3 compared to month one. There were also significant decreases in vertigo severity in month 2 and 3 compared to the first month. There were no serious adverse effects. No changes were observed in tinnitus loudness or in the Tinnitus Handicap Inventory-25 scale.
The data were encouraging and a Phase 3 clinical trial is currently underway.
There are 2 major advantages to the OTO-104 preparation compared with the standard aqueous dexamethasone solution for intratympanic use. First, the perilymph concentration with the OTO-104 is approximately 10 fold greater than can be achieved with the aqueous solution. Animal studies have also shown that the perilymph dexamethasone concentration is non-measurable 24 hours following an aqueous injection, whereas the OTO-104 maintains a therapeutic level at least 42 days after injection (guinea pig data).