AM-101 Clinical Trial — Participants Updates and Discussion

Yes, 2 weeks may have affected the results. I went to the study centre within 10 days of onset, but due to 2 week screening period and lack of appointments i got the injections on the 40th day since T onset.

If hearing damage is not repaired in 2 days it usually cannot be repaired later and tinnitus will be permanent...i think based on what i read the recovery period is same for rats and humans. And i see no reason why it should work in humans beyond 4 days.

 

Who are you accusing of having a pity party and all this "sobbing crap"? We're disguising the disappointing results of the study. Moreover, some of us may have had a lot more time and effort put into this study than you may have had. Some traveled long distances, got numerous 12, 18, 24 injections into their ears only to find it likely doesn't help at all after a certain point. Yes, it's natural to be discouraged by the results. Auris stock dropped 60% and this can have an impact on future funding for research. I'm sure tinnitus research will continue, but this is a big setback. Comparing tinnitus to a liquid biopsy is completely irrelevant.

 

I see it exactly the same! I wasn't in this trial, but it's a huge dissapointment also in term of time this candidate has taken for develping and testing.
Yes we have to wait for all data, but as it looks like now, the effect seem to be very limited.

I hope Auris has more success with one of their other drugs in the pipeline.
Imagine how much money they spent alone to register the trademark Keyzilen in all the countries.....

 

this drug may work well if injected within 2-3 days after trauma but no one had is so early

 

@Bobby B which is a failure on being able to test appropriately.

 

Granted I was trying to give some tough love but perhaps I came on a little strong. I can understand the frustration of some who spent time money on this I really Do, but at the same time complaining that their pessimism is a ten out of ten isn't helping anyone.

The point I was trying to make is medical technology advances fast now a days ten years ago liquid biopsy would be impossible but now we can screen for certain types of cancer without invasive procedures I know it's apples and oranges to T but what I was trying to say is that you never know when the next big break through on T or whatever is coming down the pipes.

We just have to keep our chin up and see what the world has in store for us.

 

Just learned the ongoing clinical trial results: http://www.fiercebiotech.com/biotech/auris-medical-off-target-tinnitus-drug-study

 

Already being discussed in the several posts preceding yours.

 

I've been following AM-101 for a long time, it's a tragic setback that it failed, but imho it's not really a surprise.

First, previous trials have been done with the oral NDMA antagonist drug neramexame which failed too with insufficient efficacy. Of course there is a difference between oral and intratympanic treatment.

Secondly, they targeted people with 'acute inner ear tinnitus', which suggests that the total damage leading to tinnitus is done in a short period of time. But for most people hearing loss is not a sudden event, but has been accumulating way before a threshold is reached which leads to tinnitus. Administrating the drug when tinnitus finally happens will only treat the small amount of damage that was the threshold.

I know for example that in animal tests for treating tinnitus they almost always simulate acute tinnitus by doing all the damage in a short time frame, by exposing the mice to loud noise.

Thirdly, they postulated the theory that tinnitus 'centralizes in the brain' when it turns chronic. Imho there is insufficient evidence of this, and if it happens it can certainly not be generalized for the entire tinnitus population. Counter evidence exists of treating tinnitus with applying lidocaine to the ear, this would simply not be possible if the 'brain centralization' theory was correct.

Again, this is my personal opinion as an amateur with an interest in tinnitus, feel free to bring in counter arguments.

Imho again, if I am correct, Auris was a bit opportunistic with this drug and their theory, hopefully it doesn't affect the rest of their research pipeline.

 

This article talk about encouraging results. Unfortunately for me (and many other tinnitus sufferers) this positive result seems to be confined to a relatively short time span after a noise incident.
But it is not al bad news.
https://www.actiononhearingloss.org...itus-drug-reaches-final-phase-of-testing.aspx

 

Yes that sounds plausible.

 

The article you linked to discusses the Phase II trial from 2 years ago. As we know now, the results from Phase III were not positive.

 

Hi @Scorpius ...I have been studing research papers on tinnitus and reading a lot on T and H ..... what you said makes sense than anything i read.....i am now thinking why didnt i get this idea after reading a lot on Tinnitus....especially your ideas about treating acute damage when the damage is cummulative.

 

Thanks for pointing this out. What I do not understand though is why Action On Hearing Loss has posted this recently.

 

This pretty much confirms my immediate improvement during my first round injections was from the Lidocaine and also explains why I did not experience the same improvement during the open label round injections. This sucks for everyone involved, including Auris, but I'm going to take the positive in it. If AM-101 was not responsible for the stretches of silence and low T, then there is hope my T is cyclical and intermittent and hopefully I will experience those multiple days of silence again. It's been a pain in the ass this past month. As far as Auris, hopefully they learn what doesn't work from this and they can use the data they gathered to look into something else. Now I don't regret my decision so much to not opt in for another round. We'll have to try something different guys.

 

It definitely makes you think about companies wanting to risk so much time and money to chase a cure when Auris has been at this for such a long time. I imagine investors can't be happy. Hopefully it doesn't dissuade others from trying but I agree that it is a setback. Though knowing what doesn't work is still progress. They only have to get it right once.

 

It seems obvious, but it actually has me worried about drug and clinical trial design for tinnitus. There has been a lot (well, relatively in tinnitus research term) of research done on how to simulate tinnitus in rodents (inducing hearing loss, training behavior on tinnitus sounds, etc) , but that might not actually reflect the situation in most humans when damage is done cumulatively over time. I can only hope they draw the correct conclusions from these results and adjust their trial designs.

Consequently I think the NDMA antagonist research angle is not a promising as previously thought, although it might help people who really have a lot damage done in a short time. It shouldn't be dismissed entirely.

 

That could be part of it. I would have been ready for my injections 1 week after onset but I had to wait 1 month.

But I have a different problem with the study and at least one of the 2 doctors that performed the injections revealed at a visit during my open label round that they at least had similar discussions internally and worries about the use of Lidocaine as a numbing agent.

It's not supposed to penetrate the ear drum, but in my case all signs point to this taking place. After having continuous T for the month leading up to the injections, I experienced silence immediately after the numbing agent and suctioning, on all 3 consecutive days of injections. However within just 15 minutes of the Lidocaine, I was in complete silence, so it's hard to toss that up to some coincidence.

Now if AM-101 did not work, then it must mean my improvement and my T definitely became intermittent on its own over time - or perhaps as I had previously thought before, the Lidocaine triggered this - since I did end up with days of silence long after the injections and I still experience this. Having said that, the Lidocaine did have an immediate effect during the procedure and who knows how long after it continued to have an affect. My first couple of weeks of the first trial showed continuous improvement.

What made little sense to me is that if they are very worried about us even doing something like using white noise to get temporary relief, I do not understand the use of Lidocaine as a numbing agent. It's been well documented as a temporary T suppressor. So it makes you wonder how many other people got some benefit initially from Lidocaine immediately after injections which later wore off.

Lidocaine has a healing benefit over the other agent and I am grateful they gave it to me but I do wonder how much it affected at least a portion of the study group that were given this. If there was any risk of it interfering with study results, I do not believe they should have used it.

Another thing worth noting. The research assistant revealed to me that Auris provides absolutely everything for the study, even vials for blood tests, they are labeled, numbered, and even the empty boxes have to be returned. I found this out because the vials used for my first blood test were expired, and had to do it again. So if they are so careful with everything, why allow 2 different numbing agents, one known to be a temporary T suppressor? Makes you wonder if there was also an additional internal research taking place at Auris or something else. You would think they would also send all trial centers one single numbing agent, and probably should not have been Lidocaine.

It's also worth noting this effect also did not happen during my open label injections when I was ~4 months in and I experienced pain overnight which I did not during the first round.

 

Has anyone had problems getting the refund of the travel/accomodation expenses? Two months now waiting and no news from them.

 

I have recently been to medical urgency, I had big increase in my T (not related to loud noise because I was for a house dinner some friends with low music and I always wear the plug when necessary) and my T is now like a strong hissing pain with still fluctuation. It kept me for sleeping during 2 nights, I had oversweat, shaking and dizziness. When I try to sleep I have like an electrical signal coming from my head which shakes my body and which keeps me awake.
In the hospital they gave me drugs for one week.
I have never been in so bad healthy condition.
I hope things will improve over time.

 

@Elgringo32
Did you mean to say you now have pain in your ears?
Hope you get better....

 

At least they gave you something. When I called the hospital during my times of agony in the first few weeks since acquiring this condition, the woman at the other side bitched me off and asked "Why the hell I was calling for something like Tinnitus". After that she went pedantic and basically told me I shouldn't call again for this.

Needless to say, the conversation didn't have a calming effect on my person.

 

I've been in 4 mental hospital since March 2015. I sleep there eat there take drugs and do classes or sleep all day. There's always loud ventilation systems and fans so I always think my Fluctuations stopped! I think I'm just back to normal central ringing so I leave but then once in my apartment I realize My T is not changing.. I would love just to have normal T without bird noises and the electric crickets and the high pitch hiss in my right ear that comes and goes switching on and off every 5 seconds. I was suicidal until I got hearing aid masker which helps mask the fluctuations! It plays a constant white noise (also can play tones and had 6 different white noise settings) it can be a life saver for fluctuations and I wear it all day and especially all night. I can't sleep without it.

 

There does seem to be a number of people including Elgringo32 and me who are in a pretty bad way post AM-101. I am bemused by the strong +ive effect score claimed after phase 2 trials and safety, compared to zero +ive effect now with some people suffering damage, life changing damage. If anybody wants to make contact please do.

 

it took nearly 4 months for me to get anything, didn't even get gas covered although they said they would. never received anything from the second round of injections

 

Let's just be positive, there is still a trial ongoing. Results are expected in Q4 says the PDF.
It's more worrying that for 2017 no really new drugs are being tested. If we can say goodbye to what does not work, we need to have a new plan.

 

With the same positive thinking, OTO-311, RL-81, SF0034 are still out there all either being tested or researched. SF0034 particularly is interesting as it is a form of enhanced Trobalt (retigabine) which has less side effect. We all heard of Trobalt having some positive result on members. So if it has less side effect, isn't that a promising drug to come that the medical fields can feel safe enough to prescribe it? I am a late man on these researches, but this is what they have talked about on SF0034 even on ENT-Today:

http://www.enttoday.org/article/new-drug-may-help-prevent-treat-tinnitus/

 

If I recall correctly, I thought Audion Therapeutics is planning to do some hearing-regeneration trials in 2017... Correct me if I'm wrong...

Besides this, we might hear more from AM-102 in Q4 as well...

 

OTO-311 / SF0034 / RL-81 are already known for some time. Besides, from what I've read RL-81 only exists on paper. Prof Thanos Tzounopoulos is doing the actual research, which is good as he puts out quite some papers, but where are the new names? Where is the evidence for nerve stimulation or other methods that we are hoping for?

 

If there was no efficacy in general what made them so sure this would only help with early onset?.Other than that it's depressing to see how powerless they are against this condition.
Even worse the condition is not taken seriously.(In society)