Date: 2011-01-27
Type of
information: Publication of results in a medical journal
phase: 1-2
Announcement: publication of results in Audiology & Neurotology reports
Company: Auris Medical (Switzerland)
Product: AM-101
Action
mechanism:
Disease: inner ear tinnitus
Therapeutic
area: Otorhinolaryngology
Country: Germany
Trial
details:
- The phase I/II study with AM-101 enrolled 24 patients suffering from persisting moderate to severe tinnitus following acute noise trauma or sudden deafness at 4 study centres (3 clinics of the German Bundeswehr and 1 private ENT practice). Their tinnitus had been refractory to a first-line corticoid treatment prior to study inclusion, and was not older than 3 months (i.e. still at an acute stage). Study participants were randomized to receive either AM-101 or placebo (ratio 2:1) in a single dose intratympanic injection. A total of 4 dose concentrations were tested under a dose escalation scheme from 30 to 810 µg/mL. Follow-up visits were performed 7, 30 and 60 days after treatment administration.
The primary objective of the study was to evaluate the safety of AM-101 delivered by intratympanic injection. Secondary objectives were a preliminary evaluation of the potential therapeutic benefit of AM-101 in the treatment of acute inner ear tinnitus as well as the determination of the systemic exposure from local drug administration.
Latest
news:
- • On January 27, 2011, Auris Medical has announced that AM-101, its investigational drug for the treatment for acute inner ear tinnitus, was well tolerated and safe in a phase I/II clinical trial and showed some first indications of therapeutic efficacy, as a recent article in the journal Audiology & Neurotology reports. The publication by the study’s principal investigators presents the design and principal results of the double-blind, randomized, placebo-controlled trial, which was conducted in 2007/08 in Germany. Overall, AM-101 was well tolerated by study participants, irrespective of the administered dose. The incidence of adverse events (AEs) was low and similar in the verum and placebo arms. They were considered either unrelated or unlikely related to the treatment. No serious adverse events (SAEs) or AEs leading to withdrawal occurred during the study. AM-101 and its primary metabolite could be found in plasma samples obtained in the first hours following treatment in small amounts only (< 0.3 ng/mL), which confirmed the favourable safety profile of intra-tympanic injection. This minimally invasive procedure allows for a highly site specific treatment with low doses and only minimal systemic exposure.
The phase I/II study, while too small to allow for formal hypothesis testing, also provided some first indications of AM-101’s efficacy. Both the subjective tinnitus loudness as measured by a 10 point visual analog scale and the minimum masking level (MML) decreased, with the verum group showing larger improvements than the placebo group. The MML decreased continuously in the active treatment arm, with a total reduction of 3.7 dB to a final MML of 5.2 dB at the last visit. In the placebo arm, the mean MML decreased as well, but this was less pronounced, with a total reduction of 1.9 dB to a final MML of 6.6 dB. The median MML dropped from 9.5 dB to 3.0 dB in verum patients, while it fluctuated in the placebo arm around the baseline level to finish 1 dB higher at 7.5 dB. There was also a trend towards improvement in a tinnitus handicap questionnaire (THI-12), however, the magnitude was clearly lower. This discrepancy is likely due to the more long-term orientation of the questionnaire and / or the fact, that patients with bilateral tinnitus got only one of their ears treated, and hence one untreated ear influenced the outcome.
Is
general: Yes
