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droxidopa trial with Dr. Lapp

Discussion in 'Active Clinical Studies' started by Rrrr, Aug 19, 2010.

  1. Rrrr

    Rrrr Senior Member

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    http://www.marketwatch.com/story/ch...igue-syndrome-2010-08-19?reflink=MW_news_stmp

    press release

    Aug. 19, 2010, 7:30 a.m. EDT Recommend Post:
    Chelsea Therapeutics Announces Initiation of Investigator-Led Phase II Study of Droxidopa in Chronic Fatigue Syndrome

    CHARLOTTE, N.C., Aug 19, 2010 (GlobeNewswire via COMTEX) -- Chelsea Therapeutics International, Ltd. /quotes/comstock/15*!chtp/quotes/nls/chtp (CHTP 3.59, +0.04, +1.13%) announced that a new investigator-led phase II clinical study of Droxidopa, an oral synthetic precursor of norepinephrine, has been initiated in chronic fatigue syndrome (CFS).

    CFS is a complex and crippling disorder characterized by extreme fatigue that is not improved by rest. In addition to fatigue, patients with CFS experience symptoms, similar to that of fibromyalgia including, weakness, muscle pain, impaired memory and concentration. Droxidopa has been shown to improve symptoms of fatigue, weakness and concentration in neurogenic orthostatic hypotension associated with a variety of conditions including Parkinson's disease, multiple system atrophy and pure autonomic failure. Droxidopa is also being studied in an ongoing Phase II trial in fibromyalgia where, during an interim analysis, an independent data monitoring committee saw meaningful efficacy in multiple treatment arms.

    Dr. Charles Lapp, a former board member of the American Association for CFS and medical advisor to the American Fibromyalgia Syndrome Association, is conducting this single-center Phase II study at the Hunter-Hopkins Center in Charlotte, North Carolina. The trial will evaluate up to 600 mg TID of droxidopa and assess the clinical efficacy using changes in Patient Global Impression of Improvement (PGI-I). In this open-label trial, approximately 20 patients will be titrated to optimal therapeutic benefit over a two-week period after which they will continue treatment for 12 weeks. The primary outcome measure will be changes in PGI-I scores from baseline to the end of the 12-week treatment period. Secondary measures include changes in the Multidimensional Fatigue Inventory (MFI), Clinical Global Impression of Severity (CGI-S), Hospital Anxiety and Depression Scale (HADS), blood pressure before and after a tilt table test.

    "As we continue to work towards an approval for droxidopa for the treatment of neurogenic orthostatic hypotension, we are eager to expand the body of clinical research supporting potential indications that could be effectively treated with norepinephrine replacement therapy," said Dr. Simon Pedder, president and CEO of Chelsea. "We welcome the opportunity to support Dr. Lapp's efforts to characterize the therapeutic role of norepinephrine in chronic fatigue syndrome and believe that a favorable outcome from this study, combined with data being generated by our ongoing Phase II trials in fibromyalgia and adult attention deficit hyperactivity disorder, will further highlight the integral role of norepinephrine as a neurotransmitter central to the etiology of a host of disorders."

    About Droxidopa

    Droxidopa, the lead investigational agent in Chelsea Therapeutics' broad pipeline, is currently in Phase III clinical trials for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) in patients with primary autonomic failure -- a group of diseases that includes Parkinson's disease, multiple systems atrophy (MSA) and pure autonomic failure (PAF). Droxidopa is a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally. Droxidopa is also being studied for the treatment of fibromyalgia and adult attention deficit disorder in two ongoing phase II trials and completed a phase II in intradialytic hypotension (IDH) study with positive results.

    About Chelsea Therapeutics

    Chelsea Therapeutics is a biopharmaceutical development company that acquires and develops innovative products for the treatment of a variety of human diseases. Chelsea's most advanced drug candidate, Northera(TM) (droxidopa), is an orally active synthetic precursor of norepinephrine initially being developed for the treatment of neurogenic orthostatic hypotension. In addition to Northera, Chelsea is also developing a portfolio of metabolically inert oral antifolate molecules engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders, including two clinical stage product candidates: CH-1504 and CH-4051. Preclinical and clinical data suggest superior safety and tolerability, as well as increased potency versus methotrexate (MTX).

    This press release contains forward-looking statements regarding future events. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include risks and costs of drug development, risk of regulatory approvals, our reliance on our lead drug candidates droxidopa and CH-4051, reliance on collaborations and licenses, intellectual property risks, our need to raise additional operating capital in the future, our history of losses, competition, market acceptance for our products if any are approved for marketing, and reliance on key personnel including specifically Dr. Pedder.

    This news release was distributed by GlobeNewswire, www.globenewswire.com

    SOURCE: Chelsea Therapeutics

    CONTACT: Chelsea Therapeutics:
    Investor/Media Relations
    Kathryn McNeil
    704-973-4231
     
    lnester7 likes this.
  2. Rrrr

    Rrrr Senior Member

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    has anyone heard of this med or tried it?? this is the first i have heard of it.
     
  3. dsdmom

    dsdmom Senior Member

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    Yes, I have heard of it. My neurologist @ UMASS has been involved w/ their trial for orthostatic hypotension. He wanted me to be part of it but I don't meet the criteria for OH - my bp is just low all the time - it doesn't drop on standing to meet OH criteria. He seems to think this will be a good drug choice for me though once it is approved. I'm happy to see that they are looking @ it in CFS - which means not just for dropping bp on standing.

    I actually am very much looking forward to having this drug approved. It's been in use in Japan for a long time and is considered very safe. Of course I always have problems with drugs so we'll see...but I haven't been able to tolerate florinef or midodrine. Which, as a side note, may be withdrawn from the market relatively soon. At least the brand name - the jury is still out on generics.

    Anyway, I see the above as a very good thing!
     
  4. sensing progress

    sensing progress Senior Member

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    Which may be withdrawn from the market? Florinef or midodrine?
     
  5. Rrrr

    Rrrr Senior Member

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    midodrine may be withdrawn.
     
  6. Navid

    Navid Senior Member

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    did anyone try this drug yet? if so, can you share your results...hopefully good : )

    thanks
     
  7. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Interesting!

    The only drugs that really helped me with OI (and they helped a lot) were norepinephrine re-uptake inhibitors. They also normalized my temperature. I've heard of trials of this one. Hope it goes through and hope it won't be wildly expensive! (that is unlikely!). I tapered off the others because of expense and getting better.

    Midodrine was horrible for me too.

    Sushi
     
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  8. August59

    August59 Daughters High School Graduation

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    Sushi - Have you tried Savella? Have you tried Cymbalta? If so, was it very expensive?
     
  9. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Hi August,

    I did try cymbalta--low dose (I think it was 20 mg.) along with strattera. They helped with OI a lot--particularly stattera which is a norepinephrine reuptake inhibitor. But they were very hard to titrate up to even the low dose--it took about 6 weeks of opening the capsules and very slowly titrating the dose up.

    I stopped them because 1) a no longer needed them, and 2) they are extremely expensive. I haven't tried Savella but I know it has a quite different formula from Cymbalta. I didn't try it because I don't have nearly as much need of OI support now, and I prefer to take the minimum of drugs. Both these medications had to be tapered off very slowly as well--taking several months.

    Hope that helps,
    Sushi
     
  10. sensing progress

    sensing progress Senior Member

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    I have never heard norepinephrine being related to OI. Can you elaborate on this Sushi? Any idea why these NRIs helped you?
     
  11. Gingergrrl

    Gingergrrl Community Support Volunteer

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    I am reviving this old thread re: Droxidopa as it is a few years old and am trying to figure out the current status of this med. My cardiologist mentioned that Droxidopa is a good alternative to Midodrine and just something that we could keep on the back burner for the future.

    We did not discuss it in detail but when I googled it, I got info which implied that Droxidopa is not FDA approved in the United States. Is this accurate and is there anyone on PR (in the US) who is taking Droxidopa?

    I'd also like to hear from anyone who had tried this med (anywhere in the world, not just the US) and how it worked for you? Was it prescribed to raise low BP or for other reasons? I read on-line that it can cause tachycardia which is the last thing on earth that I need so I am hesitant to try it but am curious to learn more.

    Also, does anyone know if it acts on the same mechanism as Midodrine (I think it is called an alpha 1 agonist but I could be wording it wrong) or is it a totally different mechanism?

    Thanks for any info!
     
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  12. Denise

    Denise Senior Member

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    Droxidopa (brand name Northera) was approved in Feb 2014 for use in this country. These are some links for info:

    http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm386311.htm

    http://reference.medscape.com/drug/northera-droxidopa-999898

    http://www.lundbeck.com/upload/us/f...ORTHERA Availability Press Release 9.2.14.pdf

    As I understand it, some clinicians (who treat this illness) are considering droxidopa in hopes that it lowers resting heart rate.
    The people I know who are on it have not been on it long enough to determine if it is of benefit or not
     
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  13. Revel

    Revel Senior Member

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    Have you joined the Dinet forum yet, @Gingergrrl? You may find some helpful info there on Droxidopa/Northera. Not been on there lately, but I remember discussions on the subject in the past.
     
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  14. Gingergrrl

    Gingergrrl Community Support Volunteer

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    @Denise Thank you for all that info which definitely clarifies that it is FDA approved in the U.S. After reading it, I am not sure if it is right for me as I have low BP all the time, vs normal BP that drops when I stand. I have weird autonomic issues that are all over the map which include orthostatic intolerance and POTS but they are not consistent and POTS well controlled with beta blocker.

    What is consistent is that I have low BP all the time but I have never fainted and rarely feel dizzy. For me, it presents with overall weakness, shortness of breath with exertion, and chest tightness/pressure. It sounds from the links that Droxidopa can increase tachycardia and angina type symptoms so maybe I am better to stick with Midodrine? I need to discuss this more with my cardio at next appt.

    Denise, I know you said that your friends who take it have not been on it long enough to determine a benefit but I was wondering if they have had any bad side effects? Also, do they take it for low BP or another reason? No worries if you don't know the answers.
     
  15. Gingergrrl

    Gingergrrl Community Support Volunteer

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    @Revel, I actually have not yet had a chance to look at or join the Dinet forum but am planning to do so soon. I think it will be really helpful info for me and just haven't had time yet but need to make it a priority. Are there lots of people over there who have tried Droxidopa/Northera?
     
  16. zzz

    zzz Senior Member

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    Droxidopa is converted to norepinephrine by the body; it is a norepinephrine prodrug. However, droxidopa apparently can cross the blood brain barrier before being converted into norepinephrine; norepinephrine cannot cross the BBB.

    Since droxidopa is converted to norepinephrine and appears to have no pharmacological activity of its own, it does indeed act as an alpha(1) agonist, in the same way that midodrine does. For this reason, somnolence would be expected to be an occasional side effect of droxidopa, as it would for all alpha(1) noradrenergic agonists. Although somnolence is not listed as an adverse reaction in the prescribing information for droxidopa, it is listed as a side effect in other places, such as this recent study, in which 4.9% of the people taking droxidopa experienced somnolence. For this reason, people who experience somnolence on midodrine would most likely experience it on droxidopa as well.

    As for tachycardia, the current prescribing information does not mention this as a side effect. In fact, the Pharmacodynamics section of the prescribing information states the following:
    Usually, the current prescribing information has the most accurate info about a drug. In this case, there is conflicting information from a number of sources on the Web (including Wikipedia) These sources state that droxidopa is converted into both norepinephrine and epinephrine (adrenaline). In this case, tachycardia would be expected to be a side effect. However, I found no reports of this. It would appear that the prescribing information is correct, and that droxidopa is simply a prodrug for norepinephrine. As such, it has various side effects related to the action of norepinephrine; these can be found in the prescribing information. However, it appears to have fewer side effects than midodrine.
     
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  17. Denise

    Denise Senior Member

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    I think discussing with your cardiologist is a good idea. (I always keep a running list of questions and documents to take to appointments. Often I highlight things on the documents to focus on points in them - rather than overwhelm with the entire document but to have the whole document so that healthcare professional sees the quality of material being cited.)

    Another group to check out might be:
    http://www.dysautonomiainternational.org/
    (Don't know if they have a forum.)

    The people I know on droxidopa have been on it for a short period of time and have not noticed side effects (at this point). I believe that their BP is fairly normal.
     
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  18. Revel

    Revel Senior Member

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    Sorry @Gingergrrl, I didn't pay much attention to the content of the Dinet threads on this subject, just remember that there were a few. It was being recommended for those with orthostatic hypotension, but not necessarily POTS. It was a bit hit and miss for the latter, more success with hyperadrenic POTS, not so much with other 'subtypes'. Hope I'm making sense, had to be sociable for 3 hours today, not really with it right now :ill:
     
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  19. Gingergrrl

    Gingergrrl Community Support Volunteer

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    @zzz @Denise and @Revel Thank you all for the additional info and I will respond tomorrow when I am more awake!
     
  20. Gingergrrl

    Gingergrrl Community Support Volunteer

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    @zzz

    zzz, Thank you and you answered exactly what I was wondering. So it sounds like Droxidopa works the same as Midodrine and (in my case) could therefore cause sedation at a higher dose and probably not work any better for me than Midodrine. I will definitely discuss this with my cardiologist in Nov.

    That is good to know and Wikipedia is one of the sources that I read which talked about tachycardia. I guess I should stop looking to Wikipedia as a source of info. I do not have any side effects from Midodrine except that when I go above 2.5 mg it no longer works and causes me extreme sedation/sleepiness.

    @Denise I do keep a running list of questions for my cardio and bring everything to appts so I am focused to save time. Thank you for the link and I have a lot of dysautonomia websites to check out as soon as I have time. It sounds like the people you know might have been given Droxidopa for another reason if their BP was normal?

    @Revel, thanks and you are making sense and i hope you are feeling better today!
     
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