Boehringer's schizophrenia med boosts cognition in phase 2

Maybe this has been posted already as it’s from September.


Hmm I wonder how different it is from Glycine supplements:

“The treatment, BI 425809, inhibits a protein called glycine transporter type 1, or Gly-T1. As its name suggests, the protein transports the neurotransmitter glycine.”


If I read the paper right GlyT1 keeps glycin levels within a range

“GlyT1 operates bidirectionally: it decreases synaptic glycine concentration when operates in normal mode and releases glycine from glial cells as operates in a reverse mode.”


Lidocaine (a common pain killer found in arthritis creams) also inhibits GlyT1. I think I’ll start treating my arthritis with Lidocaine creams :grinning: and see what happens!


So how many iq points will be increased?

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My psychiatrist promised me to get into the phase 3 trial of this GlyT1 inhibitor. He already wanted me to get into the phase 2 trial, but it was cancelled in Germany. There is some lag due to the lockdown, but he hopes that I can start in May. All participants in the phase 2 trial getting the 10 mg dose have experienced an improvement of cognition. I don’t know exactly which parts improved, but maybe verbal learning and memory is one of them as BI 425809 was first developed as an alzheimer drug.

The only relevant side effects seem to be a reduction of the red blood cells in some patients.


More about how BI 425809 might work

  1. The paper is called “Glycine release from astrocytes via functional reversal of GlyT1”. The paper shows a nice diagram about how high dopamine in SCZ might affect GlyT1

  2. This second paper (given the first) shows how GLyT’s might be in a feedback loop with Dopamine
    Modulation of striatal dopamine release by glycine transport inhibitors - PubMed

The papers are hard to read so I might have it wrong.

I was trying to figure out if glycine supplements, or conversely a glycine light diet, would be a good idea on BI 425809. I can’t tell, so if someone else wants to give it a go I’d appreciate it . . .


There is an article about the phase 2 trial with BI 425809: Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study - PubMed Unfortunately, I don’t have access. Fleischhacker is a big name (also for Cariprazine) and Lancet is a very good journal.

Can’t wait to get this med.


According to that article, the greatest improvement in the MCCB test has occurred in processing speed, problem solving (mazes) and working memory. It was significant with 10 and 25 mg, with a slightly less improvement for 25 mg. The difference was not noticeable in the PANSS (note that most of the items of PANSS are for positive and negative symptoms, less for cognitive), but they conjecture that this is because of only 12 weeks treatment. The phase 3 study will last 26 weeks.

My psychiatrist estimates that the trial will start in late summer for me.

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It has a Wikipedia page now: BI 425809 - Wikipedia
And this is the phase 3 clinical trial I will be included to: Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-3) - Full Text View - The latest news from my psychiatrist was that it might start in June.

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Good news: It seems that my initial screening for the trial is at the end of Juni or beginning of Juli, and approximately 2 weeks after that, I can get the first dose. If I’m in the placebo arm, there will be a follow up trial where I could get verum.


Good news: I will be included in the phase 3 trial Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-3) - Full Text View - I will receive my first dose in the week of October 11, and the pre-screening is in September.


Are they recruiting in the US?

I don’t know. Try to contact Boehringer Ingelheim from the mailto: link at Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-3) - Full Text View -

According to it’s restricted to Germany and VR China, but I don’t know if there aren’t any more study centers.

Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-3) - Full Text View - now lists more study partners, including one in California. I don’t know if there are more sites to be added.


I’ve had my prescreening on Monday. They performed the whole MCCB. Next visit 2 weeks after this, first dose on October 4.


Second visit (1a) today. There is the possibility of a follow-up study, starting at visit 11, where you definitely get the real drug, regardless of whether you had placebo or not. This is great! Of course, I will participate! :slight_smile:


I have already taken 4 doses since Monday. No effects, no side effects up to now. My psychiatrist told me that I can expect effects after 6 weeks if I get verum.

BTW: The only relevant, uncommon side effects seem to be light flashes before your eyes and less red blood cells (occurred in some of the patients receiving 25 mg in phase 2, whereas phase 3 is testing 10 mg, which also had the greatest improvement in phase 2).


I guess I’m in the placebo group. So I have to wait until ~May.

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Starting from tomorrow, I will get BI 425809 for one year, guaranteed verum. This is a follow-up trial. I still think that I had been in the placebo group.

I’m so curious what improvements I will experience and when they will manifest.

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