MightyMouse

I'll do my best to be there and tweet...would be only the 3rd tweet of my life despite a twitter account that is at least a few years old

skin rashes can also come from other things like your laundry detergent, soap, lotion, shampoo, etc. Did you change anything like that recentlY?

Also, keep in mind that some stomach remedies also contain asprin, especially the ones that fizz in water like Alka Seltzer.

I'm actually seeing a subspecialist soon for my gi issues--persistent break through reflux despite multiple medications (nexium 2x day, pepcid at night with the nexium, plus benedryl 50mg, singulair, and zyrtec daily; and i have a long list of medication reactions too. I will be asking the new guy about the possibility that this is histamine problem.

My favorite too... I'm a thrill seeker... faster, higher, crazier the better.

And, here's another article about the same study--which appears to have been completed by Dr. Philip Low (Mayo)

See article for results here

My Beighton score is 5, but I do not have EDS. Rather than ask you're pcp, have you considered getting a rheumatologist consult? They are more likely to be able to make a good differential diagnosis (that is, be able to tell one hypermobility disorder from another--for me, mine is related to short stature/mild form of dwarfism, although it looks very much like EDS).

Nina

I would like to just say that it's like the most effective treatment for YOU. There are so many different etiologies (reasons your body works differently) of the groups of disorders we have here that there is no one clearcut "best" or "most effective" way to treat. Treatment effects are tied directly to exactly WHY your autonomic systems are misbehaving. I have a collage defect, so my organs jostle around a lot with high impact activities like running. I do well with light to moderate exercise like yoga, weight training, pilates, etc., but running 5K could quite literally kill me--the last time I tried I partially collapsed a lung and spent 2 days in the hospital. Just saying. For some of us, vigorous exercise is contraindicated.

Please read here http://www.dinet.org/NCS/ncs.htm (from the main DINET site)

"What is neurocardiogenic syncope?

Neurocardiogenic fainting usually occurs while standing. Emotional stress, stressful condition and pain may trigger an episode, especially among the young (Shah, Gupta & Lokhandwala, 2003). The onset may be abrupt or associated with warning symptoms such as fatigue, weakness, nausea, sweating, pallor, visual disturbances, abdominal discomfort, headache, pins-and-needles, lightheadedness or vertigo (Deering, 2003). Presyncopal patients may also complain of palpitations, vomiting, disorientation, and difficulty speaking clearly or coherently (Grubb & McMann, 2001, p. 60.). Other symptoms that may present before a faint include feeling either warm or cold, tremors, yawning and having a bluish/purple or red coloring to the skin (Alboni, Brignole, Menozzi, Raviele, Del Rosso, Dinelli, Solano & Bottoni, 2001).

During the faint "seizure-like" activity may occur (Grubb, Gerard & Roush, 1991). This convulsive activity is thought to be distinct from a seizure disorder."

actually, some people do experience seizure-like episodes with some types of autonomic dysfunction--others here sometimes experience paralysis

I personally use it in salads b/c I don't really like to drink it straight. I usually put it on thiny sliced cucumbers, sliced grape tomatos and just a little bit of sweet onion sliced too--I add a little honey to the cider, with some water, salt and pepper. Yum

As for probiotics, I learned the hard way that the comercial brands have an ingredient I can't tolerate: inulin...it's a laxative. I found an organic brand w/o inulin--it's called Primal Defense, and has really been helpful in keeping my guts in order. I did pretty poorly on philips colon health...and there was a store brand I used too... both caused me gi distress.

Actually, no, it's highly unlikely that they have any real living people looking at the forum at all. Software likely does all of it. And yes, while we have members only able to contact each other directly here via pm, as well as are the only ones able to see your signature lines and profile, this is still a PUBLICLY VISIBLE forum. That's why we remind people all the time about the fact that EVERYONE who wants to see what you're writing here can see it.

I like my Mio

Oh, and for me, the most stabilizing things for my h/r are high salt diet, high fluid, and although I hate hate hate them...support hose. Not even the rx one, just some that I got from one the places people here have used to order online (can't remember name)

Yep. I have that too. Not all the time, as I'm mostly in tachy, but I've been sustained in 50's while walking (I knew b/c I was wearing a heart rate monitor). When it's low, I feel horrible--nauseated to the point of feeling like I'm going to vomit.

Elegiamore, and others, you must know that many of us with chronic or even fatal disorders frequently experience isolation, loss of friends, loss of contact with family, etc. For me, I swear there were times when if it weren't for my cats, I would have really descended into depression. For those of you who are so inclined, in many places in the US, there are free public services who will make visits to the homebound--and frankly, I'd rather have a person who is paid or volunteers to visit make visits with me than have no one at all. Places I think people could look to would be their own city or county public services, churches, Meals on Wheels or other similar organizations. For those with Medicaid or eligible for medical assistance, paid home care may be provide through those groups--and may both provide help with daily living activities and meals as well as at least some regular social contact. In planning for the day when I'm unable to care for myself, these are the kinds of things I think about.

Two suggestions: one is to go into a Sephora store and have them help you--they should know the bases for the perfumes and allow you to give them a sniff to see if they're even a smell you'd like to smell again

Second, consider just getting some essential oils from the health food store--they should have lavender oil, which is really lovely. I sometimes mix it in unscented body oil (sesame base or almond base). I've also purchased essential oils online from vitacost as well as from puritainspride and have had good experiences with both (I tend to shop online b/c shopping in a store is not a fun activity for me).

Nina

Awesome. Glad it worked--did you end up swapping out which browser you're using?

Chelsea Drops While Trying To Prevent Falls

April 10, 2012 http://seekingalpha.com/article/487471-chelsea-drops-while-trying-to-prevent-falls

On March 28, 2012 Chelsea Therapeutics (CHTP) received a complete response letter (CRL) from the Food and Drug Administration (FDA) for the company's new drug application (NDA) for Northera (droxidopa) to treat people suffering from symptomatic neurogenic orthostatic hypotension (NOH). In the CRL the FDA asked Chelsea to conduct another study which can demonstrate the drug continues to work for patients over a two to three month period.

Trial 306b Waiting in the Wings

Investors will undoubtedly be wondering if the 306b study Chelsea is currently conducting might be sufficient to demonstrate the durability of effect the FDA wants to see. The short answer is perhaps. The longer answer is, first and foremost, Chelsea would need to negotiate with the FDA regarding the trial's endpoints. 306b does measure the mean change in the composite OHQ, the primary endpoint used in the highly successful 301 study, but as a secondary endpoint. 306b simply isn't powered to use the same endpoints 301 did. Currently, the primary endpoint in 306b is the comparison between drug and placebo on the rate of patient reported falls from baseline till the end of study.

Investors should realize there is increased trial risk with 306b because it is only enrolling Parkinson's (PD) patients while 301 enrolled patients suffering not only from PD but also multiple systems atrophy (MSA) and pure autonomic failure (PAF). Treating different patient populations increases the chances of unexpected trial results. This is further complicated by the fact that in trial 302 PD patients were the most responsive while in 301 they were the least responsive.

Assuming the company and the FDA agree on the suitability of study 306b, investors will then want to focus on whether the trial can successfully blunt the management theorized carryover effect resulting in higher than anticipated placebo responses. High placebo responses have been blamed for trials 302 and 303 failing to meet statistical significance. A quick overview of NOH and Northera is likely a good idea here.

NOH is a sudden fall in blood pressure when standing from a sitting or lying position. Symptoms include lightheadedness, dizziness, blurred vision, falling and syncope. NOH is a disorder of the nervous system resulting from a deficient release of norepinephrine. Norepinephrine is the neurotransmitter that signals blood vessels to constrict. Normally, when we stand, norepinephrine gets pumped out of our neurons and tells the vasculature in our brain to constrict. This keeps us from becoming dizzy when we stand up. When we sit back down the norepinephrine that is still in our system and was not metabolized gets reabsorbed. When we sit, the blood pressure in our brain comes back down and everything returns to normal. Northera is a precursor or prodrug to norepinephrine. When taken it is directly metabolized and turned into norepinephrine and stored in the neurons.

Study 302 and 303 both sported a withdrawal design. All patients were given Northera initially and then randomized into either a group which continued to receive the drug or a group given a placebo. The placebo group performed better than expected and Chelsea believes this is because Northera replenished norepinephrine levels to the point that the neurons stored the neurotransmitter for later use. Both trials didn't run long enough for these placebo patients to stop benefiting from having previously taken the drug.

Unfortunately, 306b is designed so all patients will receive varying doses of Northera for up to two weeks initially before being randomized to continue receiving the drug or a placebo. Fortunately, the drug vs. placebo period lasts eight weeks. Hopefully, this is more than enough time for any carryover effect to cease.

Durability of Effect

At the Advisory Committee meeting both the panel members and FDA staff felt Study 301 on its own would have been sufficient for approval but the lack of long-term benefit from 303 called this into question. Can 306b show durability of effect over two or three months? It should be able to but only if it actually exists. The interim data from 306, now referred to as 306a, showed there was a greater difference between placebo and drug after one and two weeks than at the end of eight weeks. Both 302 and 301 studies were significantly shorter than eight weeks and both yielded very good data. Management alluded to the age of the patients and hinted at the untrustworthiness of their responses. Decide for yourself the merit of this positioning. Personally, I would like a closer look at the falls data. If the rate of falls increased week after week in the drug arm then maybe we are looking at diminishing returns.

Black Box Warning

In the CRL the FDA also recommended a black box warning related to supine hypertension be included in the labelling. They indicated this warning could be removed with supportive data derived from patients while they are lying completely flat. Interestingly, the standard of care (SOC) is to measure supine hypertension on a tilt table at 30 degrees. In 306b Chelsea is collecting data based on the SOC but not while patients are completely flat.

Midodrine, the current, but lacking, SOC drug for NOH also has a warning of supine hypertension so Northera would lose a nice market differentiator if it ended up with the same warning. At the very least, Chelsea hopes to convince the FDA to use language that differentiates the risk between the two drugs since data to this point shows a much higher prevalence of supine hypertension using Midodrine than using Northera.

A New Trial?

Management hopes to talk with the FDA within sixty days about a variety of topics. Any news supporting the viability of 306b as a pivotal study will undoubtedly push the stock higher but given the challenges and risks associated with that study a new trial might be the surest way to proceed. Chelsea wants to eventually obtain a much coveted falls label claim for Northera but the FDA has already stated an additional trial beyond 306b would be required for support. A new trial enrolling the proper patients, using proper co-primary endpoints, using induction over withdrawal design, and lasting two to three months as the FDA requests sounds less risky than counting on 306b to deliver the goods. However, management may feel a quicker yet still realistic path to market is to change the current 306b trial and get it approved with the supine hypertension black box label warning.

Passing Around the Hat

Despite guiding cash is sufficient to last into 2013, the company is going to need to raise more funds. They ended March 2012 with over $50 million. Negotiations with the FDA and potential changes to 306b will require more time and money. A brand new trial would likely take two years to run and cost over $28 million.

My guess is the company will wait until late June or early July to raise cash. News from talks with the FDA about 306b might come early June and data from the CH-4051 phase 2 trial in Rheumatoid Arthritis is due later that same month. Will management roll the dice on a higher stock price after these events? I think the bigger question is what they decide to do with 306b after input from the FDA.

Chelsea Therapeutics' CEO Hosts Conference to Discuss FDA's CRL to Northera (Transcript)

March 29, 2012

Chelsea Therapeutics International Ltd. (CHTP) FDA Issues Complete Response Letter Regarding Northera's NDA March 29, 2012 8:00 AM ET

Operator

Good day ladies and gentlemen and an welcome to the Chelsea Therapeutics March 29th conference call. At this time all participant lines are in a listen-only mode. Later we will conduct the question-and-answer session and instructions will be given at that time. (Operator Instructions). As a reminder this conference is being recorded. I would now like to turn the conference over to your host, Ms. Kate McNeil, please go ahead.

Kate McNeil

Thank you, operator. Good morning and thank you all for joining us to discuss our Northera new drug application for the treatment of symptomatic neurogenic orthostatic hypotension and the complete response letter received yesterday from the US Food and Drug Administration. Our press release regarding the FDA’s decision can be found on our website www.chelseatherapeutics.com. Joining me from Chelsea is Dr. Simon Pedder, President and Chief Executive Officer; Chief Financial Officer Mr. Nick Riehle; Chief Medical Officer Dr. Bill Schwieterman; Chief Scientific Officer Arthur Hewitt; VP of marketing and sales Mr. Keith Schmidt; and our Chief Operating Officer, Joe Oliveto.

Following formal remarks by Dr. Pedder, the conference call will be open for questions. Now before I turn the call over to Dr. Pedder, let me note that some of the remarks that you will hear today may contain forward-looking statements about the company's performance, actual future results might differ materially from those projected in the forward-looking statements. Additional information concerning these factors that could cause actual results to materially differ from those in these forward-looking statements contained in our SEC filings and periodic reports under the Securities and Exchange Act of 1934 as amended, copies of which are available on our website or may be requested directly from the company. And with that said I'll turn the call over to Dr. Pedder.

Dr. Simon Pedder

Thank you Kate and thanks to everybody for joining our call today. As we announced late yesterday, the US Food and Drug Administration has issued a complete response letter related to our new drug application for Northera also known as droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension or NOH. This morning we would like to take you through each of these issues identified in last night's press release and answer questions you may have regarding the complete response letter or our path forward. Before we get into detail of the agency's response I would like to remind everyone that while we have had the opportunity to review the letter in detail, we of course have not had the opportunity to follow up or speak to anyone at the FDA.

In that respect some of our discussion will involve speculation until we consult with the agency on their recommendations. While the complete response letter identified several requests and recommendations, the principle request and the one with the greatest impact for Chelsea was the request for an additional efficacy data to support the findings of our pivotal study, Study 301 and to demonstrate the durability of effect the over a two to three-month period. The complete response letter detailed the agency's guidelines for an approval based on a single persuasive study and highlighted that Study 301 was positive and achieved a typically persuasive outcome on the OHQ, Orthostatic Hypotension Questionnaire.

They further acknowledged that that their guidance is open to the possibility of a single study approval in indications which there is an unmet serious medical need. And that NOH as a condition which is still [awaiting] symptoms with limited treatment options could be a condition for which they will consider an approval based on the results of one study. The letter also states that 301 has many of the characteristics of a single adequate well-controlled study that could make it adequate to support effectiveness.

However the agency's review of the data concluded that there were some subgroups namely women, older patients, US patients and those with Parkinson demonstrated less persuasive results following treatment with Northera and I will note separately that a majority of 301 was conducted in Ex US and that a majority of the US patients participating in the study were through consultation.

They further indicated that these inconsistencies, the results of Study 303 and 303 undercuts the persuasiveness of 301. Finally the letter raised some concerns regarding what they determined to be a disproportionate large favorable effect of one site on the outcome of Study 301. While we would agree that these results impacted the outcome of the 301 our analysis shows that consistent treatment effect is seen across the positive majority of the participating sites and that adjusted for the overall number of participants, results of Study 301 excluding the site would have been persuasive.

The letter also emphasizes the agency's interest in data that adequately demonstrates the durability of the effect. As you'll recall this was also a significant discussion point, both in the agency's briefing document and subsequent advisory committee meeting where the panel ultimately concluded the potential treatment benefits coupled with a significant unmet medical need warranted approval of Northera and outweighed the need for additional study concerning durability prior to the approval ultimately recommending approval of our NDA.

Given the need to provide evidence of durability of effect, the agency suggested an additional data supporting the NDA should be from a study designed to demonstrate durability of effect over a 2 to 3 month period and recommended we consult with the agency on the specific study design elements including endpoint measures to be used in future trials. While the FDA did not make reference to the company's ongoing Study 306 we believe that data from this trial could potentially meet the criteria for clinical efficacy and durability of effect data identified in the Complete Response Letter.

As you'll recall, Study 306b is an ongoing 10-week double-blind placebo-controlled trial evaluating Northera in patients with symptomatic neurogenic OH associated with (inaudible). The primary endpoint for this trial is the reduction in the rates of fall per patient per week. However the study is also designed to assess the benefit of Northera in the treatment population using both OHSA Item 1 which measures dizziness, light headedness, feeling faint or feeling like you might blackout as well as the OHQ composite which is a more global assessment of symptomatic and functional benefits.

Since the letter was not specific with regard to the design of a longer confirmatory study, we will need to speak to the agency regarding the suitability of 306b to meet their request. This discussion will of course involve discussion regarding the primary endpoint and if that would be necessary or possible to a co-primary endpoint including both [fall] and either OHSA Item 1 or the OHQ or change in the endpoint altogether.

Until we have these discussions, it is difficult to speculate in great detail as what will be the final path forward or the time forward towards the possible approval. However preliminary estimates suggest that given our enrolment in 306b, the time required to prepare the result with submissions, we could potentially submit a major amendment to our NDA as early as first quarter of next year. Once we have designed our path forward with the agency we will of course look to update you with more vision at the timeline through submissions and potential approval.

Now, in addition to the clinical request made by the agency there were a number of additional requests and recommendations made in the complete response letter. For the most part these are not issues that will prevent approval or time-to-market. As we indicated in the press release, the agency would like to see additional bioequivalence work in order to approve the 300 milligram capsule. Just to clarify, our clinical trials were conducted using combinations of 100 milligrams and 200 milligram capsules.

Our interest in approving a 300 milligram capsule would simply be for ease of administration and we could certainly launch with only 100 and 200 milligram capsules. Of course, given that we will be working to complete clinical requirements for approval, conducting the necessary bioequivalence work to approve the 300 milligram capsule shouldn't be an issue and we anticipate this could be really accomplished prior to an FDA approval of Northera.

Finally, the complete response letter included draft recommendations regarding our labeling. I would like to emphasize that, we did not have an opportunity to engage in meaningful discussions with the agency regarding our label. So while these recommendations are informative they are not final and would not certainly be dependent on the final outcome of future studies and the collected datasets.

As we set forth in the press release, the agency recommendation, narrowing the scope of symptomatic benefits claim to emphasize dizziness, lightheadedness, feeling faint or feeling like you may black out, as the clinical benefits associated with Northera treatment. The only other item of note in the labeling recommendations was that the FDA at this time made a preliminary recommendation to include a black box warning related to supine hypertension. However, the letter indicates such a black box warning could be reconsidered a suitable data, demonstrating lack of severe hypotension, were provided.

As you may recall this topic came up during the advisory committee at a time which we explained that, in keeping up with the standard of care and clinical practice. Patients are advised to maintain a 30 degree head-up tilt in a more supine position. Panelistsin the agency expressed interest in testing supine hypertension in patients, when they are in a fully prone position. Given the convincing nature of lack of severe supine hypotension, relative to placebo in our clinical trial, we would expect to see a similar lack of significant, severe, supine hypotension compared to the placebo in a fully prone position. We look forward to get a better understanding from the agency to the scope of the data they would be interested in seeing, in order to remove the potential black box warning from our draft label.

That said, as you are well aware Midodrine has a similar black box warning, though ultimately this is not a significant competitive disadvantage. None of the recommended label changes included discussions around the black box warning, meaningful change or meaningful change apart from pricing or potential market opportunity for Northera. We look forward at the appropriate time to continuing discussions with the agency regarding a potential label for Northera.

Finally, with respect to the complete response later from the agency, I would like to point out that beyond continuing to provide complete safety data as our clinical program progresses, the letter did not identify any outstanding safety concerns related to our NDA submission. We think this is particularly significant in the light of the briefing document issued by the agency before the advisory panel meeting and the emphasis in those documents on safety and are pleased that the data presented during the panel meeting appears to have mitigated these initial concerns related to our submission.

Before I open up the call for questions, I would like to take a minute to share our gratitude for physicians, nurses, study coordinators who conducted our clinical trial and especially the patients, who participated in medical science to help bring this drug to market by participating in our extensive clinical program to-date.

In closing, I would like to emphasize our faith in Northera remains strong as ever. The testimony we have heard from patients regarding the profound effects, they’ve experienced participating in our clinical trials is among the most moving I’ve had the privilege to hear.

Though yesterday’s response from the agency was indeed a setback, we’re committed to doing our best to help those that continue to suffer from symptomatic neurogenic OH, patients who have been waiting for long treatment options to help alleviate their mediated symptoms. We recognize that Northera may meet an unmet significant need for those patients and continue to look forward to bring in this product to these patients.

Now, I would like to turn the call over to questions. Operator?

I have never found any information on causation, but I, too need very small amounts of certain drugs in order to get an effect.

Actually, you'd be more likely to have benefit just by drinking the coffee since it's a mild vasoconstrictor...and let your body absorb it more readily that way because that's what the gut is designed to do. Just my opinion...save the grounds for you roses, blueberries and azaleas, or use it as an exfoliant in the shower.

I'm not certain if this is still the case, but there was at least one of the autoimmune tests that could only be done by Mayo Clinic. Sorry, my brain doesn't remember which test, but it was one of the ones that if you have it, it causes pots-like symptoms.

I've had many, and one during one of my events, my head hit so hard that I actually damaged the vitreous in my right eye...the stuff is like jello, so image a blob of jello that gets split when you hit. I can still see fine, but I have a spot in my vision that's permanently less saturated in color and black looks grey.

I've probably had more than 10 concussions.