Ambroxol Phase 2 results

[Parkinsonjisung]

cureparkinsons.org.uk/news/...

jamanetwork.com/journals/ja...

Open study with no placebo but interesting results. There is a larger scale placebo study currently taking places in France.

[geddy]

Ambroxol is otc in Germany- in an " n of 1" ambroxol isn't worth it

[Parkinsonjisung in reply to geddy]

What dosage were you taking?

[geddy in reply to Parkinsonjisung]

75 mg

[Parkinsonjisung in reply to geddy]

The trial dosage was 1.2g per day so it was 15times higher dose. I dont recommend trying such a high level without doctors supervision but it seems your trial didnt match the trials dosage

[geddy in reply to Parkinsonjisung]

Fwiw- there is a reason ambroxol was banned in the US

[Parkinsonjisung in reply to geddy]

What's the reason? Quick Google didnt bring up any results as to why

[geddy in reply to Parkinsonjisung]

I believe one of the side effects is drying up of the mucous membranes- not good

[Parkinsonjisung in reply to geddy]

Interesting.. I couldn't find any literature on it being banned. Just saw some possible comments on it been out of patent so theres no money in it. I understand your point though. All medication have side effects and the dosage in the trial is very high and shouldn't be trialled until further studies are done.

[geddy in reply to Parkinsonjisung]

Banned was a poor choice of words- all i knew was that it was no longer available

[park_bear]

Interesting. Six point improvement in motor UPDRS is good but it could be placebo since there was no control group. Odd that Alpha-synuclein levels in the CSF increased. Good that there is a placebo-controlled study in progress.

[jeffreyn in reply to park_bear]

From the research paper:

"The increase in CSF α-synuclein could be interpreted as an increase of extracellular export of the protein from the brain parenchyma."

[sharoncrayn in reply to jeffreyn]

Ambroxol (in massive doses but who cares) has supposedly been shown to increase activity of the lysosomal enzyme glucocerebrosidase. It is both a protein and a enzyme. Hence, some theoretical applicability to PD especially if you have the relevant GBA gene mutation which can hypothetically create a build up of the unwanted alpha-syn... Unfortunately, if you don't have the relevant GBA mutation all of this wonderful theory won't have much relevance.

Theoretical cell biology at its finest. Of course, very few really understand it, but the rest will never admit it.

[Parkinsonjisung in reply to sharoncrayn]

Sharon, I believe you have a background in clinical trials. Can you explain to me why there is such a crazy delay between a trail finishing and a paper being published? This trail finished 20 months ago and only reported results this week.

[jeffreyn in reply to sharoncrayn]

From the research paper:

"Larger placebo controlled studies are warranted."

Yes or no, Sharon?

[sharoncrayn in reply to jeffreyn]

If they insist on maintaining their original criteria for inclusions/exclusions, maintain the same dose cohorts, and maintain the same placebo, the larger "placebo" trial will replicate (it must) their failed CT within normal statistical boundaries. So, "no go for another paycheck".

Of course, if they manipulate the dose downwards to almost nothing, and change the placebo, and broaden their exclusionary criteria to exclude almost everyone except clearly very healthy individuals, they will probably be capable of manipulating the earlier results thereby proposing before hand that the larger placebo trial will improve the overall outcome of this toxic drug and justify the new trial.

It will simply show that you can make a clinical trial say almost anything you want by changing the design parameters, which is why we have a lot of useless or toxic drugs.

Sharon

[jeffreyn in reply to sharoncrayn]

This is just a wild guess, but I reckon you're not a fan of the ongoing "Ambroxol for PDD" Phase 2 trial either?

clinicaltrials.gov/ct2/show...

[sharoncrayn in reply to jeffreyn]

It should stop here.

[jeffreyn in reply to sharoncrayn]

I can't see that happening. These guys are in it for the long haul.

Study Start Date: November 2015

Estimated Study Completion Date: December 2021

[Buckholt]

Interesting. I hadn't realised that Ambroxol is an ingredient in over the counter cough/throat remedies.

[MBAnderson in reply to Buckholt]

But at 15 mg per dose.

[sharoncrayn]

Why the delays in publishing sometimes stretching into years?

Delays are usually the result of multiple levels of internal reviews (and perhaps external reviews) in the attempt to make sure no subsequent outside commentary forces a negative "redaction" or worse, a negative retraction. In addition, it isn't simply writing the results up because internal and external political pressures always exist (did the pharmaceutical company or the med center or the university or the Feds like the results, or did they want the investigators to massage the data again to see if something was overlooked?) The devil lurks in the details at times.

What about a very, very common situation where the research team never publishes anything, or simply avoids publication in print by "presenting" their findings at a conference without publishing? In that case, usually the results of the CT are meaningless, or they realize it isn't worth attempting to publish because in the floating the "drafts" to several publications to get their initial reaction, no serious publication is interested or the reviews come back questioning the results. So why go to the bother of writing anything up? In the end, the CT (usually a phase 1 or 2) dies of its own natural causes without ever seeing print that is available to the scientific community let alone the public.

Sharon

[Parkinsonjisung in reply to sharoncrayn]

Thanks for the detailed response

[jeffreyn in reply to Parkinsonjisung]

This recent article may also be of interest.

FDA and NIH let clinical trial sponsors keep results secret and break the law:

sciencemag.org/news/2020/01...

[jeffreyn]

"A larger and longer study is still required to determine if ambroxol can have any actual clinical benefits in slowing the progression of Parkinson’s."

SoPD blog post from Simon (The Ambroxol Results):

scienceofparkinsons.com/202...

[Parkinsonjisung in reply to jeffreyn]

I see someone has asked Simon why it took 18months for the results. Be interesting to see his response

[Rijk99]

My understanding is that Ambroxol is available OTC in 50+ countries including Mexico. My question: Given the safety record (they give ~1 gram/day to pregnant women) and the recent trial showed safety for 6 months at that dose for PwP, why wouldn't you take it? It seems to me that it is better than doing nothing...

[CaseyInsights in reply to Rijk99]

Here is the problem -

“And while the dose that was used in this study was well tolerated and found to be safe, it was also very high and required amazing stamina from the courageous participants (seriously, 21 pills per day! On top of their normal medication).

Efforts have been made to reformulate the drug, but with limited success thus far.”

This from SoPD blog post on Ambroxol