Efficacy and safety of AM-101 in the treatment of acute inner ear tinnitus--a double-blind, randomized, placebo-controlled phase II study.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of intratympanic AM-101 in patients with persistent acute inner ear tinnitus after acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media.

STUDY DESIGN:

Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90.

SETTING:

Twenty-eight European sites (academic tertiary referral centers and private ENT practices).

PATIENTS:

248 patients aged 16 to 65 years.

INTERVENTIONS:

Three intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days.

MAIN OUTCOME MEASURES:

Efficacy was assessed by changes in minimum masking level (MML; primary end point), loudness match, tinnitus loudness, tinnitus annoyance, and sleep difficulties on a 0 to 100 numerical rating scale, THI-12 questionnaire, and patient global impression of change. Safety was evaluated using the frequency of clinically relevant hearing deterioration and adverse events.

RESULTS:

The study overall failed to demonstrate a treatment benefit based on the change in MML. However, AM-101 0.81 mg/ml showed statistically significantly better improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media. The subgroup of ISSNHL-related tinnitus patients did not show conclusive results. The study drug and I.T. injections were well tolerated.

CONCLUSION:

The study established proof of concept for AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Patient-reported outcomes seem to be more relevant and reliable efficacy measures for assessing treatment-related changes in tinnitus than psychoacoustic tests.

• Authors: Paul van de Heyning, Guido Muehlmeier, Tony Cox, Grazyna Lisowska, Heinz Maier, Krzysztof Morawski, Thomas Meyer
• Journal: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (Otol Neurotol) Vol. 35 Issue 4 Pg. 589-97 (Apr 2014) ISSN: 1537-4505 [Electronic] United States
• PMID: 24603353 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Interleukin-1beta
• Ketamine

Topics

• Adolescent
• Adult
• Aged
• Analysis of Variance
• Audiometry, Pure-Tone
• Auditory Threshold
• Data Interpretation, Statistical
• Ear, Middle
• Europe
• Excitatory Amino Acid Antagonists (administration & dosage, therapeutic use)
• Female
• Follow-Up Studies
• Functional Laterality (physiology)
• Humans
• Injections
• Interleukin-1beta (metabolism)
• Ketamine (administration & dosage, therapeutic use)
• Labyrinth Diseases (drug therapy)
• Male
• Middle Aged
• Otitis Media (complications)
• Round Window, Ear (metabolism)
• Tinnitus (drug therapy, etiology, psychology)
• Treatment Outcome
• Young Adult