Autifony Therapeutics Phase I Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus

@attheedgeofscience ...Hey man, you are waaaaaaay better than Google for answering questions and comprehensive replies. What you said covers it for me re "preparation" for Autifony trials.

(Look forward to the "Flup." report...While I'm on a "mountains high" I don't quite feel like messing with anything right now by jumping into the $$$ and unknowns of Trobalt/Potiga. Was hoping the intrepid @benryu would be doing it a few steps ahead of me...Will reconsider in a few days or week though, as I 're-integrate' to normal life and the: "Oh shit, yeah, this T and h hassle!")
Later, and thanks again J... Best, M.

 

http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group Already posted? If so sorry... Just read it now and wasnt sure.

 

Regarding prepartion for a clinical trial, I do want to mention just a few things from a topic which is not so often touched upon - the topic of psychology and becoming a human guinea pig for a period of time.

As I hinted at earlier on, a clinical trial is not about the patient, it is about all the many future patients who (hopefully) will benefit from your participation in a clinical trial. The doctors you will meet at a clinical trial are regular doctors and you will be treated well and with respect (just as you would if you went to see your own GP). But there are also some differences. Unlike seeing your GP (where there is a level of trust between you), a clinical trial is all about adhering to protocols and procedures. That means you will be asked to comply to their standards which includes screening and tests of whatever kind they require for the clinical trial regulations. You will of course also be asked to consume what essentially is an unknown "substance X". On the paper, this can seem easy enough, but for some people, when they actually go to the clinical trial centre for the first time, it can become "a little too much". Sometimes the psychological impact does not occur until after the trial - when the person realizes he/she has just taken part in what essentially is "a human experiment".

So as a psychological preparation, I suggest remembering the following:

1) Make up your mind beforehand; read all about the trial (as much as you can) - unless there is substantial new information presented to you on the day of the clinical trial, you should already know what your decision is.
2) You will become a "test subject" - yes, but unlike animal test subjects, you can leave the trial at any time (but I don't recommend this - unless there is a medical reason for doing so; leaving a clinical trial can in itself present psychological issues later on with thoughts such as "...if only I had stayed on the trial, would my tinnitus be gone?" - especially if reading about other people's success online).
3) In return for becoming a test subject you get: free treatment, access to the very latest state-of-the-art research drugs, and a chance to get cured several years ahead of the rest of the population (at a minimal risk ie. phase I has been passed). The next time you are standing in a queue at a shopping mall or sitting in a restaurant with people around you, you will from time-to-time think to yourself: "if only the people around me knew that I am one of the first 200 people in the world to become cured of an incurable condition; I have something which they can never have - no matter how rich...". It's a pretty powerful feeling.
4) There is a risk of getting the placebo, but I suspect you may be offered the real drug post clinical trial, if so.

 

I just think the guys that take part in Phase 1 trials have to have the biggest kahunas. Hats off to whomever those guys were!!!! We all appreciate your courage. Once in phase 3, at least you can take heart in knowing safety has been ruled out, like in AM101 trial.

 

Yep, It takes some guts. But I guess the money is good too. I met a dude once who was a frequent lab rat for phase 1 studies. He did these things instead of having a summer job (he studied otherwise). It seemed kinda risky but he had tried all kinds of different new medications and he had never gotten any serious side affects except some tummy aches and dizziness.

 

@attheedgeofscience ...like I said, you are better than Google! Thanks for the additional info on "preparing for trials". I fully agree with what you refer to as the psychological aspects etc. Even though I have not been in any "official" trials I sure have been in some "unofficial" ones and head games of the placebo question, etc., etc.
THANKS! M.

 

They don't pay you to take part.

 

I can't speak for Autifony's phase 1, but in most cases they absolutely do pay human guniea pigs in phase 1 trials.
Why do you think they don't get paid?

 

Guys on AM101 will tell you they don't get paid. The benefit to you is that u get cured before the rest. How much would u give to get rid of T? And they know that. They know you'll do it for free. They might cover transport and some accommodation costs but that's it. I think gone are the days of being a paid guinea pig.

 

But yeah sure - AM101 is in phase 2 and 3. I'm not sure about phase 1. Maybe because it is more risky that they will pay u for phase 1. Autifony are in phase 2A though, whatever that means. So i doubt they'll pay you to take their pill. Guys will be queueing up for the trial and paying them to take their pill !! Sad, i know.

 

No, you see phase 1 in medical trials is for safety. They only enroll healthy people. AM 101 is in phase 3 and are doing the trials on people with T, therefore no pay. Autifony is probably not going to pay their guinea pigs in phase 2 and 3 but phase 1 is for people without T. Do you follow?

 

Yeah cool. Phase 1 is for healthy people. So i'm out.

 

This should explain it all...

http://clinicalcenter.nih.gov/participate/faqaboutcs.shtml

 

Phase 1 is done anyway. They are on to Phase 2 in September - tested on people with the condition they aim to treat ...

 

Actually that made me wonder if the definition for the phases there is what was used in AM101 and what's being considered for AUT00063. It says Phase II is for efficacy, Phase III for comparisons with other drugs. Are there rules stating the size limits for Phase II and III studies, or is it just general practice that Phase II is < 300 and Phase III can be in the thousands of participants?

 

Agreed. The fact that people get paid or not to take part in the trial is irrelevant because we are passed phase 1 anyway.

 

This would be the perfect question for @jchinnis (probably no one on this forum could explain it better).

I do have a background in financial mathematics. Unfortunately that revolves around calculus optimization, linear programming, and time series. I did study statistics and group sizes required in order to establish the power of the statisic required - but that is many, many years ago already. I honestly cannot even be bothered to figure out what it all means (today). Sorry...

https://www.ctg.queensu.ca/newinv/2013/PhaseIII_stat_2013.pdf

All I can remember is that the easiest way to boost the significance level of a test statistic is by increasing the sample (or population) size...

Testing the significance level is done in an inverse fashion, if I recall correctly. But again - not my territory...

 

Get Paid to take part in the trial ...who cares?!.....HELL I'LL PAY THEM!!!

 

Send me the account details and i'll throw in my house for free!

 

How long, do you think, it'll be before we get any positive signs of release on this? (I realize we're talking years here)

 

Search the thread for "fast track". Could be sometime next year, especially as there is no existing medicine to compare it to.

 

Next Year? That's very promising....

 

As a fellow a patient I too want the drugs to get on the market as fast as possible and Im no expert on this. However please read @attheedgeofscience posts on pg. 25. He states that drugs that get "fast-tracked" are normally for cases that are a threat to the humanity. I know that right now they are going to use medicines currently in trials for the Ebola virus, but they are doing it now when around a 1000 people have died already and from what I understood it is a quite radical step. Tinnitus not even a condition on its own (generally referred to as a symptom), is is not dangerous to anyone and it causes mostly emotional and mental problems which we already have drugs for. Needless to say that the scientists have worked for it for years and I don't see why they would want to sabotage their efforts (and risk losing a lot of money) by going commercial without going through 3 phases.

 

"emotional and mental problems which we already have drugs for" <-- yeah, drugs that cause tinnitus.

 

Ok, here is why I am optimistic: Note the authors include Dr.Large (Autifony CEO) and Dr.Roland Schaette (Tinnitus researcher who predicted a cure for tinnitus within the next 10 years). Basically this is a tinnitus research dream team.
Also note- Aut3 returned Inferior colliculus spontaneous firing levels of noise exposed animals to those similar of non-exposed. Source below as always.


AUT3, a Kv3 channel modulator, counteracts elevation of spontaneous firing rates in the auditory midbrain following noise trauma

L. L. HESSE1,4, L. A. ANDERSON1, C. H. LARGE 5, R. SCHAETTE 2, J. F. LINDEN3;1Ear Inst.,3Ear Inst. and Dept. of Neuroscience, Physiol. &Pharmacol.,2Univ. Col. London, London,United Kingdom;4Dept. of Otorhinolaryngology, Head &Neck Surgery, Univ. of Luebeck, Luebeck,Germany;
5Autifony Therapeutics
Ltd., London, United Kingdom

Abstract:
Exposure to loud noise is a common cause of tinnitus in humans, and can be used to generate
tinnitus like behaviour and neural pathologies in
animal models. Here we show that four weeks
after noise exposure, mice exhibit increased spontaneous neural activity in the inferior colliculus
(IC), and this elevation of spontaneous activity is normalized by intraperitoneal injections of AUT3,
a novel Kv3 channel modulator. CBA/Ca mice were exposed to octave
-band noise (8-16 kHz) at 105dB SPL for two hours under anaesthesia. Four weeks later, extracellular multiunit recordings wereobtained in vivo from the IC; similar recordings were made from control
mice. Spontaneousmultiunit activity in the IC was significantly higher in noise
-exposed than in control mice. Tone-response thresholds were also significantly higher in noise
-exposed mice, and distributions of characteristic frequencies and best frequencies were shifted toward lower frequencies than in
control animals. Intraperitoneal injections of 90 mg/kg AUT3, a positive modulator of Kv3.1
channels, decreased IC excitability in noise-exposed animals, returning spontaneous rates to levels
similar to those observed in control animals; no such effect was observed following injections of
vehicle. AUT3, but not vehicle, also reduced the probability of firing to clicks and maximum click
-evoked firing rates in noise
-exposed animals, but had no impact on frequency tuning or thresholds
of IC responses. In control animals, there were no significant differences in spontaneous rate,sound-
evoked firing, or tone-response thresholds between animals receiving 90 mg/kg AUT3 and
animals receiving vehicle. These results indicate that four weeks after noise exposure,
spontaneous activity is elevated in the IC; that the positive Kv3 channel modulator AUT3
counteracts this increase in spontaneous activity; and that AUT3 has minimal impact on IC
responses in control animals. AUT3 is therefore a potentially promising treatment for neural
pathologies that may underlie tinnitus.



http://www.autifonytherapeutics.com/publications/Hesse-et-al-SFN-2013-Abstract-FINAL.pdf

 

Does anyone have a phone number for Autifony in the UK? Nothing on their contact page website.

 

i don't think they want people calling them directly. They are a small pharma company

 

I know it's hard but I think we just have to be patient and not annoy them too much. We will know if this stuff works soon enough!

Rich

 

I am still left wondering why these markers are made. Has anyone even proved that t is coded in the brain after a year, therefore labeling it chronic? We have no evidence how and even when t sets in. Cannot find any research statistics on this. But yet doctors quote the year and it's too late reference all the time.

 

I am in the UK. Anybody have a link so I can contact/keep my eye on the inclusion criteria? Seriously thinking about applying for Phase II.
This is a long thread, plus hard to find info on the net re the trials or even results from Phase I.