Game-Changing "Leaky Gut" Treatment (Larazotide Acetate) will soon be available

godlovesatrier

Senior Member
Messages
2,628
Location
United Kingdom
I keep debating if I should take more.

As for safety I don't think anyone knows.

I believe I took 4 500mcg caps a day and felt better. I'd rather take 3 though.

Recently have had a bit of a relapse but not sure why yet.

As for profound healing no idea. I'd assume it works quite fast. But once a day is unlikely to be enough you're certainly not replicating the phase 1 trial. Phase 2 should complete soon which would give you more data.
 

bad1080

Senior Member
Messages
433
I'm not sure about Europeans ones, but there are a couple of good Chinese vendors that ship to Europe. And by good I mean that people from this forum bought their products, tested it at a lab, and it came out as a high grade product.
any hints or links as where to find said vendors?
 
Messages
4
we are lab testing a source of raw powder from China right now. Will be sent to the lab next week once I hopefully have enough payments in.
(I have tested 11 substances from that supplier all legit - so I assume this one is as well)
Hello, I know this thread is fairly old but did you ever find a trustworthy source for Larazotide?
 
Messages
28
That clinical trial has failed.
It is now marked "Terminated by Sponsor" which you can see here:
https://clinicaltrials.gov/ct2/show/NCT03569007

And the company involved issued a press release two months ago saying it had failed (in corporate pharma speak, of course, they never used the word "failed", but it clearly did fail):
https://feeds.issuerdirect.com/news-release.html?newsid=4598003219390084
My understanding is that it did not fail; instead, the company lacked the resources to actually conduct the Phase 3 trial.

The interim analysis was conducted by an independent statistician, with the sole purpose of re-estimating the treatment group size required to detect a statistically significant clinical effect of larazotide, utilizing patient data from the study.

Based on consultation with the independent statistician, 9 Meters has determined that the additional number of patients needed to determine a significant clinical outcome between placebo and larazotide is too large to support trial continuation. The interim analysis included the first approximately 50% of the initial target enrollment and followed the completion of the 12-week double-blind efficacy portion of study.


If I am reading and understanding this correctly, this means that the Phase 3 never happened, and we will therefore never know whether Larazotide would have worked.

Further, when I am reading between the lines, the message is this: "The resources needed to do the Phase 3 exceeded the potential profitability of Larazotide as a drug."

This was a great disaster because larazotide held/holds potential not only as a drug for Celiac Disease, but for many or maybe most or even all autoimmune diseases.
 

joshualevy

Senior Member
Messages
167
Unfortunately, NameHere's analysis is wrong for several reasons. I'll walk you through what happened to explain why his hopes, assumptions, and "between the lines" are not correct, and this is just a simple research failure.

Before a study starts, one of the biggest questions, and one of the hardest to answer is: how many people to enroll in the study. Recruiting, treating, and following people is the main expense of a trial, so choose a too big number, and it is too expensive, but if you end up with too few people, then your trial is underpowered (there are not enough results to determine an outcome). There is no mathematical formula which will tell you the right number of people to enroll, because this number depends on the results you see.

For example, if everyone in the treated group is cured, and no one in the placebo group is cured, then you don't need too many people, because the results are so stark. However, if 80% of the people are not cured, and some people get better in the treated group, but a few people get better in the placebo group, then you need a much larger trial in order to get a clear answer. So you don't know how many people you need until you see the results, and you don't see the results until you have finished the trial. So it requires some very human experience, skill, and common-sense.

So these researchers though they needed a 300 person clinical trial. They organized and funded a 300 person trial. However, when they got half way through, they decided to check their progress by doing an analysis of what had happened to the first 150 people. The results were not clear. Maybe too many people were not cured (in both treated and placebo groups). Maybe too many got better in the placebo group or got worse in the treated group. We will never know. However, with the data from 150 people, and comparing the treated to placebo groups, they could see that they would not get a statistically significant result, even with 300 people.

My real summery is this: After 150 people, they ran a statistical test of the results so far. They realized that the current results were unsuccessful, and furthermore, were so unsuccessful, that even if the second 150 people were better, they would not be good enough. They knew they had an unsuccessful trial, so they cut their losses, and stopped right then.

This happens all the time. I've seen it many times. The only unusual thing is that they did an analysis at the half way point. Many studies don't and get all the way to the end before they announce failure.

I think you were confused by this statement:

Press Release said:
The interim analysis was conducted by an independent statistician, with the sole purpose of re-estimating the treatment group size required to detect a statistically significant clinical effect of larazotide, utilizing patient data from the study.

The treatment group needed to be bigger because the results were so bad. They are choosing their words very carefully in order to confuse non-researchers, but the meaning is clear: the size will not work, because the clinical effect is so small/bad. They can't detect a good clinical effect in the people already in the trial.

So lets go through two of your thoughts:

My understanding is that it did not fail; instead, the company lacked the resources to actually conduct the Phase 3 trial.

No. The phase 3 study started, and even completed the efficiency phase with 150 people. At that point, statistical analysis showed that it had failed with 150 people, and would likely have failed with 300 people, so they stopped it. Of course, the company could have tried for a 450 person study, a 600 person study, etc. However, since they failed at 150, it seems dumb to continue. You could argue that if they had 3x or 4x the money, they could have continued the trial longer and longer. Sure, but that is not the real problem. They real problem was bad results from the first (pretty large) group of people.

Further, when I am reading between the lines, the message is this: "The resources needed to do the Phase 3 exceeded the potential profitability of Larazotide as a drug."

Absolutely not. There is no information on potential profitability of Larazotide. What there is, is a finding that it did not work in the first 150 people treated, and therefore was unlikely to work for the next 150 people treated. I guess you could argue that a treatment that does not work will not be profitable, which is true, but not what you meant.

Remember, in real life, in real clinical trials, and especially not in diseases like ME/CFS: not everyone is cured and not everyone gets better or worse. In real life, some get better, and some worse, and some stay the same. What you want, overall, is more people in the treated group doing better than those in the placebo group. This is the heart of statistical significance. You are comparing better, worse, the same, in two different groups. If the results are stark a small sample size will show it. If the results are small, you need a larger size. If the results are not successful, then a large sized study will still be unsuccessful.
 
Last edited:
Messages
28
However, when they got half way through, they decided to check their progress by doing an analysis of what had happened to the first 150 people. ...with the data from 150 people, and comparing the treated to placebo groups, they could see that they would not get a statistically significant result, even with 300 people.

My real summery is this: After 150 people, they ran a statistical test of the results so far. They realized that the current results were unsuccessful, and furthermore, were so unsuccessful, that even if the second 150 people were better, they would not be good enough. They knew they had an unsuccessful trial, so they cut their losses, and stopped right then.
Where does it say this? I would like to know, definitively, if this is what happened.
 

joshualevy

Senior Member
Messages
167
Where does it say this? I would like to know, definitively, if this is what happened.
  • If you read the Clinical Trials Registry, which is the NCT link in my post #74 which you quote in #105, it says that the study planned to use 307 people.
  • If you look at the press release that the company put out which you quote in your post #105, it says that the analysis was done with about 50% of the patients, so that is about 150 people.
  • They also say "interim analysis" which means the study was underway when it was done. This was not a pre-study analysis.
  • They also say "additional number of patients needed to determine a significant clinical outcome between placebo and larazotide is too large to support trial continuation" which tells us several things:
    • Clinical outcomes are successes, so there is not enough data now to show a success. In clinical trials, if you don't have enough data to support your hypothesis, you are unsuccessful. There is no wishful thinking of the form: if I just had more data, it would prove I'm right. You have the data you have. It was not enough.
    • It also says the 150 people in the remainder of the study are not enough people to show a success (that is the "too large" phrase)
    • The "trial continuation" phrase tells us (again) that the trial was underway when this analysis was done.
  • The phrase "too large to support trial continuation" means the drug failed. After all, they want to the trial to succeed and will continue it as long as the chance exists. This phrase means that these researchers (strong supporters of the drug working) now believe that it will not work.
  • It is true they do not use the words "unsuccessful" or "failure" or anything so simple and straight forward, but that is just because they are trying to spin this for their support base. They want and need continued support, so they phrase it in a very misleading way. This is the moral equivalent of a politician saying "we fought hard" rather than saying "we lost" or a coach saying "we gave it all we had" rather than "they beat us".
 
Messages
28
Indeed, clarity is needed.

I see where it says 50% were in the interim study, but as a person unfamiliar with how clinical trials are conducted, I am uncertain how to interpret this. Especially in light of this contradictory statement:

"This study follows a Phase 2 clinical trial in 342 adult patients with celiac disease who had been on a gluten-free diet for at least 12 months, which concluded that larazotide 0.5 mg significantly reduced symptoms of celiac disease."

A definitive statement was never made about it one way or the other.

As a person with celiac disease who found relief for only 2-3 years from the gluten-free diet, but who has been suffering with significant fatigue and brain fog (CFS/ME?) for the past ~7 years despite the gluten-free diet, with new non-specific symptoms and positive but non-specific autoimmune blood markers added every few years, I (and many others also I'm sure) would like to know the following:

1. Did Larazotide acetate in fact fail?
2. If so, why did it fail? In what way did it fail? A published paper detailing how it failed, in what way it failed, and why it failed, would satisfy my curiosity in this matter.
3. What does this mean for people with refractory celiac disease?

Prior to this trial, there was much anticipation and build-up about the potential of larazotide, not only in celiac disease but also for autoimmune diseases in general. I read many published papers about these topics, as I'm sure many others did. It was supposed to work. Why didn't it work? What have we learned? And what now?

We are just left hanging...
 
Last edited:
Messages
28
Hip, I did not mean "we are left hanging" in the sense of "what can I try instead," I meant that we are left hanging in the sense that we do not really know what happened with the study, but we want to. Or at least, I do. It is extremely important to learn from failures, learn why something failed, so that true progress in knowledge can be made. This will move us closer to the truth--closer to the cause of this and other illnesses.
 
Back