AM-101 TACTT1 Results Released

No pro. Gary Soon or Later something its going to come out to fight this beast.I hope......

 

See below (everything in italics is quoted information - incl. the diagram).

Phase II Study Abstract

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.

Phase II Adverse Effects

Treatment-emergent adverse events were reported by similar proportions of patients across the treatment groups with no apparent clinically relevant differences in frequency, intensity, or relationship (Table 6). Local events accounted for greater than 50% of reported AEs and related mostly to anticipated transient changes in tinnitus perception and hearing after the tympanotomy. In 93% of cases, the eardrum was already fully cicatrized at Day 7. For 1 patient in the placebo group, the paracentesis was still open at Day 90; however, the patient was asymptomatic and declined a restorative intervention.

Seven patients experienced a total of 9 nonfatal serious AEs (SAEs), of which 4 occurred in the placebo group. All SAEs were considered either not related or unlikely related to treatment. In the placebo group, 1 patient died because of cardiomyopathy (considered unrelated). A total of 5 patients discontinued the study drug administration because of severe AEs: 3 in the placebo group (injection site discomfort, vertigo, and tinnitus) and 2 in the high-dose group (tinnitus and tympanic membrane hyperemia). All of these cases were resolved.

I have now. But, I am not sure whether that would give people like yourself any more "comfort" in terms of making a decision. People who hesitate about making a medical decision tend to "invent" reasons for not going through with the procedure one way or another. And that's also fine; experimental medicine is not for everyone.

I agree with your statement (to some degree); I see - from time-to-time - some pretty poor advice given on this site. And that's problematic when dealing with medical issues, I think. On the other hand, going to a doctor for advice is no guarentee for reliable advice either (believe or not). Doctors are actually pretty bad at their job - all things considered (mainly because medicine is a field with many variables and because human biology remains one of the most complex disciplines on Earth). But still, doctors are fairly incompetent at what they do (with the exception of surgeons and ER personnel). So at the end-of-the-day, patients are their only (and last) line of defence.

 

Thanks ATEOS. Where do you read from this chart for increased T? Is it on the line:
Ear and labyrinth disorders
Tinnitus ............ 15(18) 10(12)
How do you then interpret this if it is increased T? Is it that 15 out of 18 experienced increased T?
Same for deteriorated hearing. Where do you read those results from the chart?

 

In statistics, "n", represents the population. The population in statistics is your number of patients in each group. [You also have something called sampling (from a population) which can be used to infer certain qualities about the population (without having to consider each and every individual of the population - which be time consuming for large n).] n is a "true" statistic, therefore. The validity of the conclusions drawn from the data depends on the size of the population. The larger the n-value, the better (n-value of phase II < n-value of phase III, generally; phase III data is therefore more reliable in terms of assessing the efficacy of treatment). I am not going to go into the details about statistics because I have a background in pure/applied mathematics rather than statistics.

The population, n, is mentioned at the top of each category. So for high dosage AM101, n = 84, and out of those, 15 experienced adverse effects in terms of tinnitus, giving a percentage of 18. "%" is indicated in brackets. That's how to interpret the data.

But since only 4 people experienced severe adverse effects during treatment for n = 84, I would not be too worried about the increase in tinnitus (I would strongly assume it was not permanent for the 15 patients in question - ie. compare it with the placebo group which experienced a similar increase).

My advice is to stop worrying about statistics, and read the conclusion drawn by the report (which I highlighted in green earlier on):

The study drug and I.T. injections were well tolerated.

That's all you (and others) need to worry about. Reviewing statistics is not beneficial - unless you know what you are doing (and most people don't when it comes to medicine).

Take care.

 

ATEOS... As usual, you find, post, share...solid, detailed, impeccable information. For me at least, it saves much effort sifting through 'stuff' to find the wheat in the chaff.
Thank you! Your generosity in time and patience here is very much appreciated.
Zimichael

 

Hi ATEOS. Thanks for your response. It helps to know what these figures actually are. As you say, you need a degree in medical statistics to interpret them correctly.

 

hey hey hey hey hold on something just got me excited

I was pretty disappointed to find out that, as a 16 year old, I would be ineligable for further trials. But in the publication abstract for the phase II results on Auris' site, it says

"Patients

248 patients aged 16 to 65 years."

Sooo... Are 16 year olds eligible or what? I need to get on this quick because I'm not gonna be acute for much longer...

 

The MML didn't change, yet there were improvements in tinnitus loudness, annoyance, and sleep difficulties...

Isn't the MML directly related to the loudness of the tinnitus?

 

Hi Snake Plissken. I am sorry to hear you have T at such a young age. Contact the nearest trial center and ask them. I see you are in Chester. Is that in the UK?

 

Not all people said it does not work. @cullenbohannon and @Fish reported improvement after the treatment, I believe.

 

Urtica had good results as well. And posters on reddit I think.

 

Thanks @cullenbohannon for that reminder. I forgot about @urtica. Yes, he also reported that he was in the follow up study, that he was getting the real drug and that his T is hardly noticeable. So that is 3 people that have benefitted that have taken part in the trial. Do you have those links to the reddit posters? Tx.

 

Here you go @SteveToHeal

http://www.reddit.com/r/tinnitus/comments/1m1kiy/follow_up_on_am101_study_i_participated_in/

 

Thanks @lapidus

That makes 4 success stories from AM101 that I now know of.

 

Does anyone know if there's any potential long term effects that AM-101 (esketamine) could have on your hearing?

 

It's hard to say. Probably not much, as esketamine is used for anesthesia and has been for many years without documented side effects involving hearing.

 

I'de like to add to what @Hudson said, bear in mind that this is a very short term treatment (3 shots), the side effects will be very minor & temporary.
The only known side effects associated with similar drug molecules are dependant on the frequency of consumption.

As example, the ketamine (similar molecule) can be used for recreative purposes and only with a high frequency of consumption it may induce ulcerative cystitis or affect the memory.

It's a common side effect for heavy use of drugs messing with dopamine receptors and it is VERY VERY unlikely to happen for a one time use.

 

Yeah, I'm close to the Manchester centre, I'll try contacting them.

@attheedgeofscience

You say all the side effects are transitory, but in Fig. 2 of the results, we see some people in the high-dosage group had "significantly worse" T after 90 days, compared with none in the low-dose or placebo groups. Is this not cause for concern?

 

If you're making alusion to this:
*IMAGE WAS DELETED ON 3RD PARTY SERVER*


Don't worry too much, the n is very small & I would just say that this is statistical noise and an issue with the reliability of measuring T. It's all about perception and we don't have a quantative way to measure T. except the MML and it can be super volatile... The authors actually admit it several times.

What's more important I think is first the proportion in terms of positive response, and the linear correlation between dose & effect:
*IMAGE WAS DELETED ON 3RD PARTY SERVER*


EDIT: for the people freaking out about the idea of acute T. if you have a closer look to the article they say that this is an arbitrary concept and will conduct further research to give a better definition of T. Now what I can say is that there is no evidence of a statistical differences in the tested group (3 months).

In other words all samples seem to come from the same population. So no matter when they had their OM or AAT the behavior is the same and I expect time to have a small impact on the product efficacity.

We will have the confirmation (or not) of my asumption when they will do inter group t-test . I am pretty sure this is what they have in mind when I look at the design of the statistical study.

 

I had an interview with a consultant to see if I was suitable for this trial a few weeks ago. The upshot was I decided not to go ahead with it - the reason being my T is not that bad and at the moment doesn't cause me major distress - I had to weigh that against the possibility however remote of the treatment making it worse.

I can understand why someone with very intrusive T would struggle to understand someone passing up the opportunity but I figure if this drug is proven effective in the long term it will be effective for all not just those with recent onset T and in the meantime I can live with it.

 

People on reddit had better experiences with it

 

I just received my first injections today. Basically an hour ago so my ears are still full feeling. I go in for another set of injections tomorrow, and then the final injections on Friday.

I'll keep everyone posted on my progress and try to answer any questions I can.

Is there a better place to post these kind of entries? or is this the best place?

 

If I was 18 id definately take part in it.. it makes me so mad. They have a treatment that could fix something horrible, but only for a limited amount of time, and i wont have access to it in that time. I even emailed them about it and they just responded "Unfortunately, study participants need to be at least 18 years old."

 

Hello,

I am new to this forum and tinnitus (unfortunately). I woke up with a ringing in my right ear about 10 days ago. Went to ENT on day 2 and he put me on prednisone, which did not seem to help and caused me severe insomnia. I stopped taking the meds after 6 days.

After calling around and researching, I received a call yesterday from a local ENT office asking if I wanted to participate in the AM-101 phase 3 trial.

I feel I am in desperate times. I have difficulty sleeping, my stress level is way up, quality of life is down, etc.

I'm trying to decide if I should go ahead and begin the screening process for the trial. I have never participated in a clinical trial and I am very apprehensive but my life has been severely impacted by the ringing and if a few shots in the ear would take care of it (or at least lessen the severity of the ringing), I think I would be willing to take the risk.

Being new to this, I am curious as to what other longer-term sufferers think of my predicament and opportunity.

Thanks!

 

Absolutely do it. Youl be fine, few on here did it you can read and ask around. If your T is seriously impacting your life, then deff give it a shot, ofcorse discuss it with the ent for qualifications but your ten days in so that could be good cause your still in the acute stage.

 

http://bangordailynews.com/2012/12/03/health/drug-makers-step-up-search-for-hearing-loss-medicines/ They offered am111 on the streets to random people?

 

http://www.hotstockmarket.com/t/279565/ears-auris-medical-holdings Came across this dont know if it was posted... Are these people that work at auris?

 

Second round of shots went well today. It's been about six hours, my ears still feel a bit clogged. The tinnitus is a bit more annoying than it has been.

They told me I should notice the improvements in about 2 weeks.

Though I and they don't know if I'm getting the drug or the placebo.

3rd round of shots tomorrow.

 

Good luck @earsnothappy , I am eagerly watching your reports.

@StayPositive , I will be making my final decision to join to AM-101 trial this weekend. I have a call scheduled with Kathy in Havertown, PA on Monday.

She mentioned to my that 3 people have participated in the trial at their location.

Person #1 is doing "fabulously" (her words)
Person #2 dropped out of the trial on their own
Person #3 did not see results after the first round and was considering the follow up treatment with the real drug. I assume this is you, @StayPositive ?

 

Great news re Person#1.
If Person#2 is @StayPositive, good luck man!
I wonder why Person #2 dropped out?

All the best @robs re your decision.