I have read on the internet about a clinical trial with Dimebon. It is supposed to be something that is used in Russia as an antihistimine. I would like to know is anyone in the states would have any idea how to purchase Dimebon?

To my knowledge it is not sold here. The company will be starting a phase III trial in the second haldf of 2008. You can contact them at http://www.medivation.com.

M. Berry:

If you are still interested in Dimebon, here is a portion of Medivation's 1st Quarter Earnings Call where David Hung, President & CEO, discuss's the positive results from the Phase II trial and plans for the Phase III trial for which they are currently recruiting. Seems as though there will only be around 200 patients from US, of which 2/3 should receive Dimebon. But it is only a 6 month study and participants will be able to get Dimebon upon completion. Requires an MMSE 10 to 24. Dr. T's neighbor doctor, Jeffrey Cummings is quoted in the call.

Sounds promising, however as others, if the trial goes well, it will not be available until 2010.

http://seekingalpha.com/article/78671-medivation-inc-q1-2008-earnings-call-transcript?source=yahoo&page=-1

http://www.clinicaltrials.gov/ct2/show/NCT00675623?term=dimebon&recr=Open&rank=1


Medivation, 1st Qtr 2008 Earnings Call : RE: Dimebon Status

Dimebon is an orally available small molecule that we are currently evaluating for the treatment of mild to moderate Alzheimer's disease or AD, and mild to moderate Huntington's disease. Our data suggests that Dimebon has a novel mitochondrial mechanism of action that makes it a promising potential treatment for neurodegenerative diseases including Alzheimer's and Huntington's.
During the first quarter, we held a successful end of Phase II meeting with the U.S. Food and Drug Administration. The FDA recognized our previously completed trial of Dimebon in patients with mild to moderate AD as pivotal and allowed us to proceed to a confirmatory pivotal Phase III trial. This is a significant step forward for Medivation as we now have clear regulatory guidance on the pivotal trials required to seek marketing approval for Dimebon in the U.S. Based on this meeting, we plan to begin a pivotal confirmatory Phase III trial of Dimebon in mild to moderate AD and are on track to begin the trial this quarter.
The results of our first pivotal trial of Dimebon in AD were robust. After six months of treatment, which is the duration of dosing used to approve every drug on the market for mild to moderate AD, Dimebon showed significant improvement above placebo on five of the five end-points measured, including the Alzheimer's Disease Assessment Scale-Cognitive subscale, the ADAS-cog, and the Clinician's Interview-Based Impression of Change plus the caregiver interview, the CIBC-plus. These are the two end points that have been used to approve every drug registered in the U.S. and Europe for mild to moderate AD.
The physical significance of Dimebon's effects on both these key measures was achieved with the P value of less than 0.0001. After a year of dosing, Dimebon caused even greater overall treatment effects over placebo than have been seen after six months. This increasing treatment effect over time is suggestive of disease modification. Other longer studies with additional end points will be required to bear out and make this claim.
In March and April, we presented results from three separate sub-analyses of data from this first pivotal trial of Dimebon in AD. These analyses yielded additional findings demonstrating broad improvements in behavior, daily function, and memory and thinking in Dimebon treated patients, as well as critical caregiver related benefit over a one year period.
At the annual meeting of the American Association for Geriatric Psychiatry last month, Dr. Jeffrey Cummings, the Augustus Rose Professor of Neurology at the University of California, Los Angeles and the Director of the UCLA Alzheimer Disease Center, presented neuropsychiatric data showing that Dimebon treatment resulted in improvement over placebo at 8 of the 12 sub-domains of the neuropsychiatric inventory or NPI.
Improvements were seen in depression, apathy, hallucination, irritability, and motor disturbances. These findings are significant because behavioral problems in AD patients are some of the most distressing issues facing caregivers and one of the leading causes of institutionalization of Alzheimer's patients. In the presentation by Dr. Cummings, the behavioral improvements caused by Dimebon resulted in a significant decrease in caregiver distress at both six months and one year.
At the annual meeting of the American Academy of Neurology, which was held two weeks ago in Chicago, additional sub-analyses were presented. Dr. Rachelle Doody, Professor of Neurology and Effie Marie Cain Chair and Alzheimer disease researcher at Baylor College of Medicine presented data showing that patients taking Dimebon experienced significant improvement in their ability to perform daily tasks over a one year period compared to placebo. This improvement allowed caregivers to save an average of nearly one hour each day caring for patients after just six months of treatment.
The benefits of Dimebon were seen in the most basic human functions such as eating and toilet use, as well as in more complex activities such as phone use, conversation, meal preparation, traveling, keeping appointments, reading, and using household appliances. In some, Dimebon improved the overall function of these patients.
In addition, Dr. Steve Ferris, the Gerald and Dorothy Friedman Professor of Psychiatry at New York University and the Director of NYU Alzheimer’s disease center presented data demonstrating that Dimebon treated patients showed broad improvement in the key aspects of cognitive function over a one year period compared to placebo. The improvement occurred not only in memory and language but also in more complex functions such as awareness of time and place and praxis, the process of getting an idea and initiating and completing a new motor task. To our knowledge, clinical effects of this breadth, magnitude and durability in AD have not previously been demonstrated with any other drug in a well controlled one year study.
We remain on track to begin our confirmatory Phase III AD trial this quarter. Given the robust results seen in our first pivotal trial, our guiding concept with the second pivotal trial is to change as little as possible in order to maximize our chances of confirming the prior results. For this reason, the primary end points, duration of treatment and patient inclusion and exclusion criteria in a confirmatory pivotal trial are all substantially identical to the previous trial. The primary differences are that the confirmatory Phase III trial will be global and will test two doses of Dimebon.
The Phase III trial will enroll approximately 525 patients with mild to moderate AD at sites in the U.S., Europe, and South America. We expect to have 60 to 80 sites, approximately a third to half of which will be located in the U.S. Patients will be randomized to one of three treatment groups, the same dose of Dimebon study in our first pivotal trial, a lower dose of Dimebon, and then placebo. Patients will be treated for six months and may not be taking any other Alzheimer’s disease drugs during the trial.
After completing six months of treatment, all patients including placebo patients will be offered the opportunity to receive Dimebon in open label extension. The co-primary end points are the ADAS-cog and the CIBC-plus. Two out of three patients enrolling in our confirmatory Phase III trial will receive Dimebon immediately and all patients will have the opportunity to receive Dimebon in our open label extension after a period of six months. We believe that significant numbers of AD patients and caregivers will find enrollment in our Phase III trial to be a very attractive option.
We expect to conclude this confirmatory Phase III study in 2010 to enable submission of a marketing application later that year. This quarter, we also began a Phase I trial to test the safety and tolerability of Dimebon when given to AD patients concurrently with Aricept, the leading marketed AD drug.
We also completed this quarter 18 months of dosing in the open label extension of our first pivotal AD study. In our open label extension, all patients who completed 12 months of dosing on a blinded basis were allowed to receive Dimebon on an open label basis for an additional 6 months for a total human [ph] period of 18 months. In other words, patients previously receiving Dimebon continue to do so. All patients previously randomized placebo cross over to Dimebon. We will be presenting these data at a medical meeting next quarter.
We are excited about the progress that we've made in the clinical development of Dimebon for AD and are working hard to bring it to market so patients can gain access to a drug that might truly improve how they and their caregivers live with this terrible disease.


Ira

Lets hope that Medivation can move this along quickly. The preliminary results sound encouraging. It is currently expected to be ready for market in 2010.

June 9 /PRNewswire-FirstCall/ -- Medivation, Inc. (Nasdaq: MDVN - News) today announced it has initiated dosing of patients in its second pivotal Phase 3 trial of the investigational drug Dimebon(TM) in patients with mild-to-moderate Alzheimer's disease (AD). The international, double-blind, placebo-controlled safety and efficacy study of oral Dimebon is known as the CONNECTION study.

Dimebon Showed Statistically Significant Benefit Versus Placebo on All Key Efficacy Endpoints in First Pivotal Trial

Here is the link to the press release on Yahoo:

http://biz.yahoo.com/prnews/080609/aqm035.html?.v=56

Ira
vend95@yahoo.com

Does anyone know if this particular drug is obtainable on the open market in Russia.My mother has med-sever Alzheimers and we have nothing to lose in trying any drug available.I really do hate this disease , it is so debilitating.

Are there any trials ongoing in the UK and if there is , where can I register?

Any help appreciated..

Chris,

There has been discussion of Dimebon on the
'Enbrel for Alzeimers' thread. Dimebon is no longer available OTC in Russia and we cannot obtain it in the US. There are trials going on the US currently. Do a search on the Internet for possible clinical trials in the UK.

Good Luck,

Jeanne

I had a ridiculous thought regarding Dimebon, that perhaps Rxman, swarfmaker, or someone else who may have a Pharmacological / medical background could comment.

In light of the fact that Dimebon seems promising as a posible treatment for AD, but it is no longer manufactured as an antihistamine. Is it possible that Dimebon was very similar to some other 1st generation OTC antihistamines, which are currently on the market. By any chance could any of these produce similar results?

First-Generation OTC Antihistamines

Brompheniramine (brand names: Dimetapp Cold & Allergy Elixir, Robitussin Allergy & Cough Liquid)
Chlorpheniramine (one brand name: Singlet)
Dimenhydrinate (one brand name: Dramamine Original)
Diphenhydramine (some brand names: Benadryl Allergy, Nytol, Sominex)
Doxylamine (two brand names: Vicks NyQuil, Alka-Seltzer Plus Night-Time Cold Medicine)

Obviously one would have to consult with their physician, but could it make any sense to try Dimetapp, or Dimenhydrinate to see if one notices any improvements?

Just a thought?

vend95@yahoo.com

A very good thought vend95.

I asked a similar question of rxman several days ago...I wanted to know what the ingredients of Dimebon were and if there is a
possibe generic version still available, or at least something similar. Dimebon is now off the market so I wonder how we could get that information. Any ideas anyone?

I was also wondering the same thing and googled the chemical composition of Dimebon and came up with this link http://www.thechemblog.com/?p=559
You should be able to do the same with any medication and most drug inserts also show the molecular structure. We just need RX man to interpret.

Erin

Good find Erin,

Do we have any chemists / pharmacists that can match Dimebon up with any US currently available OTC antihistimes or does it's molecular structure make it totally unique such that similar antihistimines have no chance of achieving similar benefits?

Dimebon = C21H25N3

2,3,4,5-Tetrahydro-2,8-dimethyl-5-(2-(6-methyl-3-pyridyl)ethyl)-
1H-pyrido(4,3-b)indole

I tried to find out the name of the Russian Manufacturer and more details regarding Dimebon's chemical make up by looking at Medivation's annual report from 2004. It didn't have what I was looking for, however it did contain a lot (~8 pages) of interesting background information about Dimebon, clinical data, phase ii, and experimental results on mice compared to aricept, Namenda, ect. Here are the first couple paragraphs and the link for those interested.


From 12/31/2004 Annual Report
Medivation "Our Dimebon Program"

Background

Dimebon is a Russian drug which was approved in 1983 by the Ministry of Health of the Soviet Union for use as an oral antihistamine. According to the manufacturer of Dimebon sold in Russia, more than 28 million doses of the drug have been manufactured for human use in Russia since Dimebon’s approval in 1983. Dimebon has been used in Russia for the treatment of allergic conditions such as allergic rhinitis and allergic dermatitis.

In the early 1990s, scientists at the Institute of Physiologically Active Compounds in Chernogolovka, Russia, a scientific institute of the Russian Academy of Sciences, began screening large libraries of chemical compounds for NMDA receptor inhibition, based on data that implicated dysfunctional NMDA receptor activation in Alzheimer’s disease. The Institute of Physiologically Active Compounds researchers identified a class of molecules, called gamma carbolines, which they believed to inhibit the NMDA receptor. Based on their further research, the Institute of Physiologically Active Compounds scientists concluded that Dimebon, a gamma carboline derivative, interacted with the NMDA receptor in a manner that rendered it a suitable candidate for further development work. The Institute of Physiologically Active Compounds researchers later performed experiments showing that Dimebon also appears to inhibit cholinesterase—a drug target which became validated in 1993 when the FDA approved the first purported cholinesterase inhibitor for the treatment of Alzheimer’s disease—and mitochondrial permeability transition pores—a drug target which, while not validated for the treatment of Alzheimer’s disease, has been linked to Alzheimer’s disease in the published literature.


http://www.sec.gov/Archives/edgar/data/1011835/000119312505027186/d10ksb.htm

vend95@yahoo.com

I've had a couple of conversations with the clincial trial folks. I live in a trial city and wanted to get my mother in. Unfortunately she's taking Namenda. You have to be off any Alzhiemers medication for 3 months.

That's unfortunate because it looks like Dimebon could help a lot of people if it passes this 3rd phase of the trial. If anyone with a trial city cares for someone with Alzhiemers and can GET them qualified for the trial they'll have a 2 in 3 chance of getting Dimebon (instead of the placebo) for 6 months. The great part is, after 6 months .. they say the patient can keep taking Dimebon. Even after the trial is over.

Keep us posted on any news about that possible antihistime alternative. Surely the Russsians weren't the only ones to inadverntly stumble upon the active ingredients.

If anyone is interested:

Here is the link to the chemical structure of Dimebon.

http://www.chemspider.com/Chemical-Structure.170644.html

What is wrong with the FDA? If dimebon sold OTC to the tune of 23 million doses in Russia without significant side effects. Why would they tie up this drug for 2 yrs testing it again? Granted, it's being claimed as treatment for something other than a antihistimine, but really... What harm could it do to let those with no other hope to have access to it now? It's already proven itself to be safe.

TeresaM:

I just posed the same exact question/frustration to someone. It doesn't seem to make sense. Medivation has actually been testing Dimebon for AD since 2004 with promising results, so it will be a total of (6) years to get this approved for AD, after it was used safely for 20 years.

vend95@yahoo.com

Trying to figure out the FDA is opening a can of worms the size of Everest. They can be a nightmare and there seems to be so much political lobbying going on that its getting ridiculous. However, the FDA is inundated with a million requests every year and I can see why it may take them some time to approve drugs for specific uses.

synapse@cerebralhealth.com
Developer of Memeron

Good points especially about the probable safety of Dimebon. The sad part is that you can't get into the clinical trial if you're taking any kind of Alzhiemers drug. I think they pose that restriction not because of safety concerns but in order for them to prove that Dimebon ALONE improves Alzhiemers the patient has to take 100% Dimebon for 6 months.

I asked them if I could take my mother off Namenda for 3 months so she could qualify for the trial. They did not recommend doing that.
Which makes sense. The only option so far Dimebon-wise any of us has until 2010 is to find an alternative.

I would think off-hand that the American company that purchased rights to the 20 year old Russian drug searched long and hard for alternatives before securing rights to Dimebon.

This is the same thing as with Enbrel, which we KNOW works for many of our Loved Ones. Dr. Tobinick has patents to protect people who can be injured by doing an injection such as this without training. The patents didn't hold up anything, they're not even valid out of the United States. Doctors just don't want to be liable for anything if it hasn't been through these double blind studies. Sometimes, they have to bend the rules, especially with proof as as we have with Enbrel. FDA needs to open their eyes regarding both Perispinal Etanercept (Enbrel)and Dimebon. Many people could have been saved in the last couple of years if the medical society had just listened to Dr. Tobinick. At least he's saved people in the meantime by treating them. He chose to keep treating his patients, as many as he could, and just keep publishing his results and get the word out. Without limiting to people with certain MMSE scores or medications. Dimebon marketers are going about it the "clinical trial" route, and it's taking just as long if not longer for us to get it. Can't they at least open it up to the public for off-label use like Enbrel? I wonder what taking both Enbrel and Dimebon would do for our loved ones...Dimebon has been known to cause depression, Enbrel has been known to make everyone happier! I would like to see how they work together!

Felicia

Thx for that post. I haven't heard of Enbrel but I'll check it out. And, a word about FDA clinical trials .. Long ago me and my mother particiapted in Pzar's Alzheimer's clinical trial. They believed that their "already on the market" Lipitor could treat Alzheimers. They weren't trying to prove it safe .. they just needed to show that it could improve Alzhiemers.

Today in 2008 we know Pizar did not prove that. Me and my mother dropped out about midway through the trial but from what I've seen they're not trying to prove to the FDA that an established drug is safe. They have to (before giving it a cures Alzhiemers label) that it's effective.

ABC news labeled Dimebon a miracle. Dimebon's in the news all the time. I don't know about "cure" but I've seen the words "halts brain death" so again, sadly I think that those 200 Americans luckly enough to get into this clinical trial will be among the first humans to survive Alzhiemers.

These posts have given me a new idea .. contacting the manufacturer itself. The drug's safe. 20 years of use in Russia. I'll see what they have to say about the possibility of at least obtaining it. Some of us have people who may not make it until 2010 so for me at least we've got nothing left to lose persuing all alternatives. Thx again for the Enbrel link. I'll check it out.

Tester---Have you considered the Elan/Wyeth 'Bap' clinical trial? I'm really excited about the potential of this treatment...Unfortunately, Charlie did not make the screening cut.

The bureaucracy of the FDA is astounding. I guess that the thalidomide incident is responsible for much of it.

I believe in the potential of Enbrel as a tool in fighting Alzheimer's and eventually will probably decide to seek treatment outside of Dr. Tobinick's network. Contrary to Felicia I believe that the only thing Dr. T is attempting to protect with his patents is his financial picture. He does not appear to have much sympathy for people with Alzheimer's. I believe that I read somewhere on the Enbrel thread that one of Dr. T's in-network doctors was willing to administer no cost (or reduced cost treatments) and was told not to by him.

That Enbrel has a 'Black Box' warning because it compromises the immune system puts it in a different class than Dimebon. Since you can only die once and Alzheimer's will eventually cause the death of our loved ones...I don't worry too much about it. As far as Felicia's statement that Enbrel does nothing to people mentally except make them happy...The jury may to be still out on that one. In reading through the text of the Alzforum Live Discussion, I came across a statement that 3 people in a study of Enbrel for RA suffered from acute psychosis.

Aside from enabling participants to be part of the cutting edge of medicine...Clinical trials supply the medication and testing free...Most even provide nominal monetary payment to participants. In my opinion...That is a better alternative than paying in-network charges of:
$700 for the initial consultation, an additional $5000 to $7000 consultation fee, and $1,000 per weekly injection (a 4 dose pack of Enbrel available at Walmart for $750 may or may not be included in this cost). The in-network physicians may be trying to quickly recoup the $5000 training fee as well as the $3000 per patient licensing fee paid to Dr. Tobinick. Even so...That is one heck of a mark up for administering an injection that could be done by an RN.

Judging from what has been reported on our Enbrel thread and looking at YouTube videos that appear to show what I consider to be 'cosmetic' improvement, I've decided that when I do seek Enbrel treatments...I'll go out of network and convince a doctor to administer a month of treatments. I'm certain that if the results are obviously positive, they will continue to administer the treatments.

Good luck.

Sorry Tester,

I have been talking about Enbrel for so long now that I sometimes assume everyone knows about it...well that is what I'm working on but it looks like I haven't done a very good job! I didn't want to get into all this here which is why I simply referred you to the Enbrel thread.

Skericheri, I think you've misread my words. I never said Enbrel doesn't do anything except make people happy, it just happens to be a very common effect. It does way more than make most patients happy, in about 80% of the people getting the treatment, it improves their cognitive abilities at least a little and then stops the progression of Alzheimer's, just like Dimebon supposedly does. It sounds like they do the exact same thing, and I am very happy about Dimebon. But, since it's not available yet, I will keep Mom on the Enbrel. Even through her recent major surgery, none of these major risky side effects have occurred in her, or any others I have had the pleasure to meet or talk to.

Dr. Tobinick is not doing a Clinical Trial, he doesn't have $100 Million dollars to sponsor it. Nobody believed him after he did his initial study, not a double-blind study. The results were so remarkable that he thought Amgen (makers of Enbrel) would would run a Clinical Trial. They refused, and it's been a block wall ever since. He just gave them a phase I trial to get things started. Amgen's statement about Dr. T is a lie, saying his work not been presented at an appropriate medical or scientific meeting, nor have they been published in a rigorous peer-reviewed medical journal. He presented it at the ICAD 2 years ago, and his work has been published in peer reviewed journals. He couldn't and wouldn't stop treating his patients. The man many think has no heart, didn't have the scientific heart to give his patients a placebo. He continues to treat patients and for those of us lucky enough to be able to get to him we are very grateful. He charges a lot, but he has his reasons and it's none of mine or anyone else's business. I'm just fighting for approval so that insurance will pay for it. I don't care about all the "other" issues right now, we need to get beyond that and help people get better.

My Mom's worth all the money we can pull together. Bottom line is medical treatments cost money, and if the insurance companies don't decide to pay for it, it's up to us. Dr. Tobinick is unable to treat everyone in the world, so he treats them one patient at a time in his office, and he trains other doctors to do the same. Yes, he's making money, but only after years of doing the studies with no compensation. He gave his time and money, now is the time for the FDA to approve this so that insurane will pay for it...that is my reason for being here, but you already know that.

Until Dimebon is available, I want everyone to know that Enbrel is there now. Two years is a very long time in the life of a AD patient...too long to wait.

Felicia

Wow. Lots to read. Thanks both of you. And, interesting point about Dr Tobinick not giving patients a placebo.

That's what make clinical trials risky. Placebo's. My mom was in the Lipitor study for months getting free "pills" all the time. Because it was a double blind test to where the prescribing doctor doesn't even know who's getting the real drug, who's getting the sugar pill .. to this day we will never know if my mother all that time as indeed getting nothing but a placebo. Unfortunately in real clinical trials placebo's have to be used. Not good news for those getting the placebo if the test drug turns out to be effective. Even with the Dimebon trial there's a 1 in 3 chance that for 6 months the patient will be given nothing but sugar pills. That's not good. If my mother misses even one day of Namenda problems arise.

Tester,

In the Dimebon clinical trial one of the criteria of getting in is that the patient is on no AD meds at all, for three months. Dimebon is for most cognition issues, not just AD, so I'm sure that rule applies as well for other prescribed drugs. Therefore, no one will be going off a critical prescribed drug. At the end of the trial, the patients will be given the real Dimebon. That's what makes it worth while.