14 replies to this topic

[hdl_1]

AEVI Genetics completed the parallel phase 2/3 trial on Fasoracetam (AEVI 001) for ADHD and released the results to the 6th World Congress on ADHD.

[b]Double-blind placebo-controlled study of the novel therapeutic AEVI-001 in adolescents with ADHD and glutamatergic network gene mutations in children and adolescents with ADHD (SAGA Trial)[\b]

[quote]
This is an exciting and novel finding in ADHD, that CNTN4 mutations have a meaningful prevalence in ADHD and are highly associated with a response to AEVI-001. CNTN4 mutations and deletions have been previously associated with neurodevelopmental delay, ASD, and other neuropsychiatric conditions. ADHD and ASD are frequently co-morbid with each other, and these new data suggest that CNTN4 mutations may be a common genetic link for these diseases. I look forward to working with the Company to study this further in children with mutation positive ADHD as well as the potential to study AEVI-001 in patients with ASD."

The recent analysis demonstrates that of the 42 patients with a mutation in one of nine genes (n=18 patients on treatment, n=24 patients on placebo), 89% of patients on treatment (n=16) had a clinically meaningful and statistically significant response to AEVI-001 in the SAGA trial (defined as a 30% or greater reduction in ADHD-RS score from baseline), vs 21% on placebo (p < .0001). Patients on treatment had a reduction in ADHD-RS of 17.6 versus 5.9 on placebo (p < .005). This subset of patients had mutations in the CNTN4 gene as well as certain GRM and neurodevelopmental genes.

More specifically, 18 patients with copy-number variation (CNV) mutations in CNTN4 were enrolled in the SAGA trial (six patients on treatment and 12 patients on placebo). 100% of CNTN4 positive patients (n=6) treated with AEVI-001 had a reduction in ADHD-RS of > 30% vs. 25% of placebo patients (p=.0027). The magnitude of response of CNTN4 positive patients treated with AEVI-001 was a 20.8 point reduction in ADHD-RS vs. an 8.9 point reduction in ADHD-RS in patients on placebo (p=.03).

"The robust response of CNTN4 mutation-positive ADHD adolescents to AEVI-001 in the SAGA trial suggests that CNTN4 associated ASD may be successfully treated with AEVI-001," said Garry A. Neil, M.D., Chief Scientific Officer, Aevi Genomic Medicine. "Based on these new findings, we are validating the prevalence of CNTN4 mutations in ASD and will further characterize the phenotypes associated with this mutation. Importantly, the Company intends to continue the development of AEVI-001 in ADHD and ASD, as well as other potential neuropsychiatric indications in genomically defined populations based on the responder analysis of the SAGA trial."

Based on the Company's study "Glutamatergic Network Gene Mutations in Children and Adolescents with ADHD (Phenotype/Genotype study)," approximately 10% of ADHD patients bear a CNV mutation in one of the nine genes. As found in the SAGA trial, the most prevalent gene in this phenotype-genotype study was CNTN4, with an approximate prevalence in ADHD of nearly 5%.

Patients bearing mutations in CNTN4 exhibited a unique and more severe ADHD phenotype. Compared to other ADHD patients, they had significantly higher rates of parent-reported behaviors suggestive of emotional dysregulation, including: disruptive behavior, anger control, risk-taking, and inappropriate movements and sounds.
[\quote]

Results:
http://phx.corporate...icle&ID=2263475

http://phx.corporate...icle&ID=2255087

All news:
http://phx.corporate...irol-news&nyo=0

[Keizo]

It is nice to see my anecdotal experience legitimized, I felt fasoracetam was very powerful when I tried it.

 

I wonder if there is anywhere one can look at blood work and whatnot. For now I'm sticking to methylphenidate because I don't want to do some permanent change to my reproductive system or anything else I might care about.

 

 

[Mind_Paralysis]

WOW!!

I've been waiting for this data for YEARS! : D Ever since I heard about the upcoming trial of Fasoracetam!

 

Now, the very specific genetic data they've published here, that's the most interesting information - this could be a very valuable tool if one could find a way to properly test for CNV's!

 

 

Alas, I have yet to see a commercial service which offers such testing...

 

...Anybody have any leads on where to get the genetic testing done?

 

I should mention btw, that my own personal response to Fasoracetam was limited - seemingly simply similar to that of neurotypicals. I also don't fit the profile of the children with CNTN4-mutations, quite the opposite, actually.

 

But still - it would be nice to know for CERTAIN.

[airplanepeanuts]

Shouldn't they be somehow convinced that Fasoracetam is reasonably safe, if they are doing human studies like that?

[Mind_Paralysis]

Shouldn't they be somehow convinced that Fasoracetam is reasonably safe, if they are doing human studies like that?

 

Actually, they are already VERY certain that Fasoracetam is safe! Don't forget, Faso was previously in extensive testing for the treatment of Alzheimers disease - on elderly multi-sick patients, and it's quite safe - at the very least like it's older cousin Piracetam.

 

Also, please note, these new studies are on CHILDREN as well - and has shown a good safety-profile.

 

Those two patient-groups are the gold standards when it comes to safety and faith in a compound, so you betcha' it's safe! = )

[PeaceAndProsperity]

Fasoracetam works in all individuals. That's why it's a drug of abuse for college/university teens.

[gamesguru]

 Fasoracetam is reasonably safe

 

is it though?  it's crazy how quickly the scene is evolving.  i just don't know how i feel about kids huddled up in the hallway, doing lines of faso before midterms.  ya know?  of course noots would be useless if the test writing wankerbots didn't put such a stern emphasis on rote learning

Edited by gamesguru, 27 April 2017 - 01:37 AM.

[Dakman]

Fasoracetam works in all individuals. That's why it's a drug of abuse for college/university teens.

What sort of effects are these people getting to use it in such a manner, I've tried quite high doses and not experienced anything noticeable ?

[PeaceAndProsperity]

 

Fasoracetam works in all individuals. That's why it's a drug of abuse for college/university teens.

What sort of effects are these people getting to use it in such a manner, I've tried quite high doses and not experienced anything noticeable ?

 

Like the irresponsible, impulsive drug addict whose username I will not mention, said, it increases motivation, concentration and some other things in high doses.

What you bought may have been junk because you should at the very least experience anxiety if you overdose it.

 

[gamesguru]

 said, it increases motivation, concentration and some other things in high doses.

 

he said the same thing about the now banned preworkout stim "Craze" and about 57 other things, none of which you can pronounce without a chemistry degree, all of which can kill you with the slightest mistaken in measuring.. a truly unique combination of personal factors string him from med to med thinking each will somehow be different from the last, but i'm afraid they just keep leaving him more and more wonky and in desperate need of a holistic approach

[dopaminerush]

What is the last news ? 

[Heinsbeans]

 

Has anybody tried fasoracetam + reboxetine? Could this combination be a viable alternative non-stimulant option for those who can't tolerate atomoxetine's side effects?

 

I really don't know what to do at this stage. I much prefer reboxetine because it's easier to tolerate, has less side effects on the heart, doesn't make me as fatigued or drowsy/sedated as atomoxetine. But I do miss atomoxetine's effects on calmness, deeper level of thinking and zen-like surgical focus. Plus, my sleep wasn't as bad on atomoxetine as it is now on reboxetine (probably because of longer half-life and lack of effects on GABA). 

 

What's interesting is that atomoxetine started to improve my mood (or numb it in a good way; kind of similar to SSRI blunting) after I got over the initial worsening of mood during the adjustment phase. I'm guessing that's somehow related to kappa-opioid antagonism/partial agonism effects. Whereas with reboxetine, it helped with mood a bit during the 1st week of honeymoon period. But after that it didn't have much effect on mood. BTW here's the summary of pharmacological effects of ATX I've compiled: https://docs.google....dit?usp=sharing

 

I want to take both reboxetine and atomoxetine which might help off-set atomoxetine's sedation but I don't think it's a good idea to mix these two meds since there's no synergy. 

 

Just to clarify, I've only tried Indian generic version of atomoxetine and not brand Strattera. I was on ~37.5mg Hypercon for about 3 months, tried 25mg Attentrol for ~1 week, 10mg Axepta for 2 days and now I'm on 2mg reboxetine for just over a month. 

 

Hypercon to me was the most easily tolerable. It felt anxiolytic, calming and sedating in a good way but it started making me overly fatigued and anti-social/reserved. Whereas Attentrol felt less sedating, cleaner and more stimulatory. But on the flip side, it was harder on the heart. I'm not sure why it felt that way but I'm suspecting it's because it contains fine powders inside the capsules as opposed to tablets thereby reaching into my bloodstream too quickly. As for Axepta, it was the most sedating/drowsiness inducing brand for me and I couldn't even tolerate more than 2 days on it.

 

Because reboxetine is the easiest to tolerate, I could probably easily increase the dosage to 8mg to get the maximum therapeutic effects. But at currently on 2mg, I feel like I'm still going to need something more for concentration, prioritisation and organisation which atomoxetine seemed to have been more effective for at equivalent/lower dosage.

Edited by Heinsbeans, 08 July 2018 - 05:25 PM.

[Mind_Paralysis]

 

 

Has anybody tried fasoracetam + reboxetine? Could this combination be a viable alternative non-stimulant option for those who can't tolerate atomoxetine's side effects?

 

I really don't know what to do at this stage. I much prefer reboxetine because it's easier to tolerate, has less side effects on the heart, doesn't make me as fatigued or drowsy/sedated as atomoxetine. But I do miss atomoxetine's effects on calmness, deeper level of thinking and zen-like surgical focus. Plus, my sleep wasn't as bad on atomoxetine as it is now on reboxetine (probably because of longer half-life and lack of effects on GABA). 

 

What's interesting is that atomoxetine started to improve my mood (or numb it in a good way; kind of similar to SSRI blunting) after I got over the initial worsening of mood during the adjustment phase. I'm guessing that's somehow related to kappa-opioid antagonism/partial agonism effects. Whereas with reboxetine, it helped with mood a bit during the 1st week of honeymoon period. But after that it didn't have much effect on mood. BTW here's the summary of pharmacological effects of ATX I've compiled: https://docs.google....dit?usp=sharing

 

I want to take both reboxetine and atomoxetine which might help off-set atomoxetine's sedation but I don't think it's a good idea to mix these two meds since there's no synergy. 

 

Just to clarify, I've only tried Indian generic version of atomoxetine and not brand Strattera. I was on ~37.5mg Hypercon for about 3 months, tried 25mg Attentrol for ~1 week, 10mg Axepta for 2 days and now I'm on 2mg reboxetine for just over a month. 

 

Hypercon to me was the most easily tolerable. It felt anxiolytic, calming and sedating in a good way but it started making me overly fatigued and anti-social/reserved. Whereas Attentrol felt less sedating, cleaner and more stimulatory. But on the flip side, it was harder on the heart. I'm not sure why it felt that way but I'm suspecting it's because it contains fine powders inside the capsules as opposed to tablets thereby reaching into my bloodstream too quickly. As for Axepta, it was the most sedating/drowsiness inducing brand for me and I couldn't even tolerate more than 2 days on it.

 

Because reboxetine is the easiest to tolerate, I could probably easily increase the dosage to 8mg to get the maximum therapeutic effects. But at currently on 2mg, I feel like I'm still going to need something more for concentration, prioritisation and organisation which atomoxetine seemed to have been more effective for at equivalent/lower dosage.

 

 

Low-dose Modafinil takes care of that sedation you get from Atomoxetine - works like a charm, my friend! Of course, you may end up sleepless from that instead... :o

 

Another option, is low-dose Vyvanse - Lisdexamphetamine, or perhaps low-dose Adderall.

 

I've used similar combos with ATX (I've got a crap-load of posts about various medication-trials) and it's works quite well.

 

 

Modafinil is the drug I personally feel was the least side-effects prone when combined with ATX.

[Heinsbeans]

Thanks, I don't think I'll be going back to Indian generic atomoxetine because I just can't tolerate them even with modafinil which I'm already taking. In fact, I'm finding that stimulants in general gives me heart palpitation side effects while atomoxetine is taking effect (aka in my blood stream). So I often have to take it at night in order to still be able to enjoy my cup of coffee in the morning. While with reboxetine on the other hand seems to work synergistically with any stimulants without heart palpitation or high blood pressure side effects.

Also, I'm starting to hear that it's a bad idea to drink caffeine while using atomoxetine. Here's the quote from addforums: 

 

Caffeine + Strattera is well discussed on here to impact the Strattera's effects. Its not just about taking away its 'punch'; it can also worsen the side-effects of Strattera or even take away from Strattera's positive effects.

 

 

 

If you google [caffeine atomoxetine site:www.addforums.com] you can find quite a lot of discussion around it. I suspect it might got to do with opioid antagonism from compounds in coffee or weird interaction to NMDA receptor from compounds in coffee such as β-Carboline and possibly caffeine.

I may try atomoxetine one last time by ordering genuine Strattera from online pharmacy to see if the Indian generics that I was taking were as good as the real thing. But it will set me back ~$60 for just 14 pills, they're very overpriced. And despite Strattera going generic, I cannot seem to find any non-Indian generic atomoxetine being sold from online pharmacies. But Edronax and Wellbutrin is very easy to find in abundance.

We need more non-stimulant alternatives for ADHD-PI. I can't wait until what the clinical trial has to say about fasoracetam. It's too bad that metadoxine failed the clinical trial. I'm keeping my eye on Viloxazine which seems to be more effective than reboxetine. https://mentalhealth...-pipeline-2015/

Edited by Heinsbeans, 10 July 2018 - 05:40 AM.

[Major Legend]

If anyone is interested - all the research on Fasoracetam for ADHD in one place here