Published Research - Pharmaceutical

[Aiken]

Ann--

Do you have a link to the first study regarding augmentation on tramadol? Or is that referencing the SSRI augmentation above, since tramadol is a partial SSRI?

(I'm hoping the "one patient" nature of the study indicates that it's uncommon. Tramadol is my only good choice at the moment. It's good to know, though, in case I start having earlier onset.)

Thanks for posting these...

[cornelia]

Aiken, the first study was done in 2006 by drs Early and Allen, says PubMed, but there is no abstract.

Corrie

[cornelia]

One of the researchers of my country has written an article. In it it says that researchers begin to think that something goes wrong within the brain with morphine-like substances in our nervous system. That could be why codeïne works for some patients.

He mentions too that researchers found that a shortage of iron gives a higher incidence for augmentation.

Corrie

[ViewsAskew]

Corrie, when I was at the conference, the doctors said they had developed an idea of why some people augmented and others did not - I'd forgotten about it. And, know I can't remember what they said. . .maybe it was iron that they said, too

[ViewsAskew]

This is really, really interesting. Zach, this is for you and any other IBSers we have on board.

http://www.medpagetoday.com/MeetingCove ... ng/tb/5762

Bascially, it links gut bacteria to IBS and RLS. . . of course this won't apply to all of us, but seems that this bacteria can limit absorbtion of iron and also cause IBS symptoms. It was a small trial, but this doc made huge inroads in the patients who tried the therapy.

[ViewsAskew]

I wonder how this matches with Randy's - rfishburn - experience with Xyrem (the drug name for GHB)

http://www.websciences.org/cftemplate/N ... D=20066287

Gamma-hydroxybutyrate (GHB) has re-emerged as a major treatment for narcolepsy. As dopaminergic transmission is clearly involved in the pathophysiology of restless legs syndrome (RLS), and GHB reduces dopamine release, one may hypothesize that RLS may occur in narcolepsy in the presence of GHB. We report a case of narcolepsy with a severe occurrence of typical RLS with GHB, symptoms never previously experienced by the subject and reversible after withdrawal.

[ViewsAskew]

Now, this is an interesting study. It was about a drug called sumanirole. I'd never heard of it. So, I searched. It took awhile, but I determined that it was pulled from studies for Parkinson's and RLS in 2004 because it didn't show any difference from placebo.

But, this new study? It showed it wasn't effective for RLS, but it WAS effective for PLMD. Hmmmmm.

http://www.websciences.org/cftemplate/N ... D=20066288


OBJECTIVE: To compare the efficacy, safety and tolerability of sumanirole with placebo in patients with idiopathic restless legs syndrome (RLS). METHODS: In this double-blind, placebo-controlled, randomized, parallel-group, dose-response study, 270 patients with idiopathic RLS were enrolled and randomized to receive sumanirole 0.5, 1.0, 2.0, or 4.0mg, or placebo. The primary efficacy endpoint was mean change of the total score of the International Restless Legs Scale (IRLS-10), a 10-item scale, from baseline to end of maintenance. Secondary assessments included polysomnography (PSG) variables. RESULTS: Treatment with sumanirole was well tolerated. Mean change in IRLS-10 showed no statistically significant change compared with placebo at any dose, although the mean change with the 4.0-mg dose was numerically greater than the other doses and placebo. PSG variables, specifically the periodic leg movements during sleep, showed statistically significant dose-related improvement in favor of sumanirole. Consistent with earlier multinational, multicenter studies in RLS, high placebo response rates were seen with IRLS-10 but not with PSG variables. CONCLUSIONS: Given data published in Parkinson's disease, the dose range of sumanirole selected here may have been too low. Alternatively, dopamine D(2) selective agents could be intrinsically less effective than agonists with combined D(2)/D(3) activity. Sumanirole demonstrated an excellent safety profile.

[rfishburn]

GHB helped me sleep very peacefully thru the night, however the morning rebound on the nervous system was hell and after a few months became unbearable, I also had joint pain but I suspect that part was hormone related now.

[ViewsAskew]

In this study, they gave healthy adults doses of opioids to see how it affected sleep. Not good news for those of us relying on opioids, as it showed that opioids increased stage 2 and decreased deep sleep and REM. Basically, it's the same situation many of us with severe PLMS were in before we started with the drugs.

http://www.websciences.org/cftemplate/N ... D=20066645

[ViewsAskew]

Good news for those who awaken in the middle of the night and can't get back to sleep (not because of RLS, but because of insomnia).

http://www.websciences.org/cftemplate/N ... D=20066649


STUDY OBJECTIVES: To assess the efficacy of zaleplon 10 mg and zolpidem 10 mg administered during experimental middle-of-the-night awakenings in patients with sleep-maintenance insomnia using objective polysomnographic measures and to assess daytime residual sedation 4 to 7 hours after dosing using sleep-latency testing. DESIGN: A randomized, double-blind, placebo-controlled, 3-period, crossover design was used to study 37 adults with insomnia who received treatment during an experimental awakening 4 hours after bedtime. Latency to persistent sleep and total sleep time before and after awakening were recorded. The primary residual sedation measure was a sleep latency test conducted hourly from 4 to 7 hours after treatment. Self-report measure of alertness and concentration and digit symbol substitution tests were examined concurrently. SETTING: Sleep disorders centers. PATIENTS: Thirty-seven adults with sleep-maintenance insomnia. Interventions: Zaleplon 10 mg, zolpidem 10 mg, or placebo. MEASUREMENTS AND RESULTS: Thirty-one patients had efficacy-evaluable data; 37 patients received at least 1 dose of study medication and were included in the safety analysis. Compared with placebo, latency to persistent sleep after both zaleplon and zolpidem was shorter and total sleep time after administration of the drugs was longer (overall p < .001, Dunnett p < .001 for all posthoc comparisons). Significant differences from placebo were not found with zaleplon in daytime-sedation measures. At 4, 5, and 7 hours after zolpidem, sleep onset on sleep latency testing was shorter than after placebo (overall p < .001 for all, Dunnett tests for posthoc comparisons p < .001, p < .001, p < .05, respectively). Self-report measures of concentration (4, 5, and 6 hours, overall p < .05, Dunnett p < .05 for each time point) and alertness (4 hours, overall p < .05, Dunnett p < .05), and Digit Symbol Substitution Test scores (4 and 5 hours, overall p < .001, Dunnett p < .01 for both time points) after zolpidem were also lower than with placebo. CONCLUSIONS: Zaleplon 10 mg and zolpidem 10 mg effectively shorten sleep latency and lengthen sleep duration after dosing, when administered during experimental nocturnal awakening. Residual sedation was not detected as little as 4 hours after zaleplon 10 mg, whereas residual sedation was detected with zolpidem 10 mg up to 7 hours after treatment. These findings suggest that zaleplon may be an appropriate treatment for use when patients awaken during the night and have difficulty reinitiating sleep.

[ViewsAskew]

http://www.medicalnewstoday.com/articles/84909.php

Rotigotine Transdermal System Shows Significant Symptom Reduction And Tolerability In Patients With Restless Legs Syndrome
Main Category: Neurology / Neuroscience News
Article Date: 09 Oct 2007 - 2:00 PDT

UCB, Inc. presented results from two Phase III pivotal trials and one open-label extension trial of rotigotine transdermal system for the treatment of moderate-to-severe restless legs syndrome (RLS). These rotigotine data showed significant drops in RLS symptoms, including changes of up to 8 points over placebo using the International Restless Legs Syndrome Study Group Rating Scale (IRLS) and a reduction in disease severity over a two-year period.

"Given the strong efficacy and tolerability seen to date, rotigotine, if approved, would provide a new and valuable alternative for many patients negatively impacted by the symptoms of moderate-to-severe RLS," said Wayne Hening, M.D., a lead study investigator and Assistant Clinical Professor of Neurology at the Robert Wood Johnson Medical School.

In the two six-month, double-blind, placebo-controlled trials, rotigotine produced clinically relevant and statistically significant reductions in RLS symptoms compared to placebo and was generally well-tolerated. An additional presentation highlighted a two-year interim analysis of a long-term, open-label extension of rotigotine for moderate-to-severe RLS, representing some of the longest safety follow-up information for a dopamine agonist in RLS to date.

In these studies, the efficacy of rotigotine was evaluated by monitoring several clinician-administered scales including the IRLS, the Clinical Global Impressions (CGI) and the Restless Leg Syndrome-6 (RLS-6). The IRLS scale measures the severity and frequency of RLS symptoms and the degree to which they affect sleep and daily life (IRLS: 0 = no symptoms and 40 = very severe symptoms). The CGI scale measures the general severity of an illness, clinical improvement or efficacy of treatment parameters. On the RLS-6 scale, patients rate the severity of their RLS at four periods during the night and day, as well as sleep satisfaction and daytime tiredness.

A synopsis of rotigotine RLS clinical data presented at the meeting follows.

Six-Month Studies in Patients with Moderate-to-Severe Idiopathic RLS

SP 790
- In a multi-center, double-blind, placebo-controlled, Phase III trial, 458 patients were studied in eight European countries

- Rotigotine was studied in doses of 1, 2 and 3 mg/24 hours over a period of six months

- The study showed a statistically significant improvement in the IRLS sum score and a clinically relevant reduction in the CGI Item-1 (severity of illness) score compared to placebo

- The mean baseline scores were: IRLS 28.1 ± 6.1 and CGI 5.0 ± 0.8 reflecting moderate-to-severe symptoms at baseline

- The net effects over placebo after 6 months of treatment were 5.1 ± 1.3, -7.5 ± 1.3, and -8.2 ± 1.3 in the IRLS and -0.76 ± 0.19, -1.07 ± 0.19 and -1.21 ± 0.19 in CGI Item-1 for rotigotine 1, 2, and 3 mg/24 hours respectively (p < 0.001 for all comparisons)

- Rotigotine was also shown to be generally well-tolerated

- The most common adverse events that were determined by the investigators to be drug-related were application site reactions, nausea, headache and dizziness

SP 792
- In a multi-center, double-blind, placebo-controlled, Phase III trial, 505 patients were studied in the United States

- Rotigotine was studied at doses of 0.5, 1, 2 and 3 mg/24 hours over a period of six months, with all doses showing improvement over placebo

- Rotigotine, in doses of 2 and 3 mg/24 hours over a period of six months, resulted in a statistically significant improvement in IRLS sum score and a clinically relevant reduction in the CGI Item-1 (severity of illness) score compared to placebo

- The mean baseline scores were: IRLS 23.3 ± 5.0 and CGI 4.7 ± 0.7, reflecting moderate-to-severe symptoms at baseline

- The net effects over placebo after six months of treatment were -2.2 ± 1.2, 2.3 ± 1.2, -4.5 ± 1.2 (p<0.001), -5.2 ± 1.2 (p<0.001) in the IRLS and -0.35 ± 0.19, -0.32 ± 0.19, -0.65 ± 0.19 (p<0.001), -0.90 ± 0.19 (p<0.001) in CGI Item-1 for rotigotine 0.5, 1, 2, and 3 mg/24 hours respectively

- Rotigotine was also shown to be generally well-tolerated

- The most common adverse events were application site reactions (27.2%), nausea (21.5%), headache (17.6%) and somnolence (12.6%)

24-Month, Open-Label Extension Trial in RLS

SP 710
- In an open-label extension of a double-blind, placebo-controlled, Phase II dose-finding study conducted at multiple centers in Europe, rotigotine, administered with optimal dose titration, showed long-term therapeutic efficacy in patients with moderate-to-severe idiopathic RLS who were treated for 24 months

- A total of 295 patients entered the open-label extension trial and 191 (65%) completed the two-year maintenance period of this ongoing trial

- After 24 months of open-label rotigotine treatment, 87% of patients were rated as only mildly ill, borderline symptomatic, or normal on the CGI Item-1 scale which rates overall severity of illness

- The "change of condition" CGI Item-2 score showed a sustained improvement from the beginning through to the 24th month of open-label maintenance

- Additionally, the "severity at bedtime falling asleep" score (RLS-6 Item 2) improved by 4.0 ± 3.1 points following optimal rotigotine treatment

- Rotigotine treatment led to a 4.3 ± 3.3 point increase in "sleep satisfaction" (RLS-6 Item 1) and a 4.9 ± 3.0 point reduction of symptom severity "during the night" (RLS-6 Item 3)

- "Daytime tiredness and sleepiness" (RLS-6 Items 4 and 6) scores were reduced by 2.4 ± 2.7 points

o All effects were first observed during the titration period and were sustained over 24 months of open-label treatment

o The most common adverse events were application and instillation site reactions (50%), nasopharyngitis (12%), back pain (11%) and nausea (11%)

"We are pleased to report these promising findings, which show that rotigotine has potential as an important therapy in the management and treatment of RLS," said Iris Loew-Friedrich, MD, PhD, Global Head of Development, UCB. "Clinical data strongly support the development of rotigotine for RLS, and we will work closely with regulatory authorities in both the United States and Europe in order to bring this important medication to market."

Neupro® (Rotigotine Transdermal System) is currently approved in the United States for the treatment of early-stage idiopathic Parkinson's disease and in Europe for the treatment of patients with early-stage Parkinson's disease and in combination with levodopa for advanced-stage Parkinson's disease. Applications for the use of rotigotine transdermal system in patients with moderate-to-severe RLS are currently being prepared for submission to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMEA).

About Neupro® (Rotigotine Transdermal System)

Rotigotine transdermal system is a non-ergolinic dopamine receptor-agonist formulated as a transdermal delivery system, a patch, designed for once-a-day application. Rotigotine is designed to mimic the action of dopamine, a naturally-produced neurotransmitter crucial for proper motor functioning. The system is applied to the skin once daily and provides rotigotine continuously to the body for 24 hours.

About Restless Legs Syndrome

Restless legs syndrome (RLS) is a chronic and progressive neurological disorder that affects up to 10 percent of the population. It is characterized by unpleasant feelings in the legs and an irresistible urge to move in order to relieve the discomfort. RLS sensations are frequently described as tingling, burning, tugging, creepy-crawly, gnawing and pulling. Symptoms typically appear during periods of rest and inactivity, particularly in the evenings and at night. This can make it difficult to fall asleep and stay asleep, thus preventing recuperative sleep and often leading to daytime fatigue and reduced alertness.

About UCB

UCB, Brussels, Belgium is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialisation of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology - UCB focuses on securing a leading position in severe disease categories. Employing more than 10,000 people in over 40 countries, UCB achieved revenue of 3.5 billion euro in 2006 on a pro forma basis. UCB is listed on the Euronext Brussels Exchange and owns approximately 88% of the shares of SCHWARZ PHARMA AG. SCHWARZ PHARMA AG (Monheim, Germany) is a member of UCB Group.

[ViewsAskew]

This may not apply to us in any way, but high phosphorus levels were associtated with hemodialisys patients who had RLS. Wonder if anyone has ever tested those without kidney issues to see if phosphorus is involved?

http://www.renalandurologynews.com/RLS- ... cle/96364/

[ViewsAskew]

This is new to me - anyone know what this drug might be or how it works? The company it's associate with is Jazz Pharmaceuticals.

http://money.cnn.com/news/newsfeeds/art ... 2007-1.htm

[mackjergens]

Here is a link for the med by Jazz that states its for RLS, its another SSRI antidepressant.

http://www.rxlist.com/cgi/generic/fluvox.htm

[ViewsAskew]

I only have a minute, but the links last word is "fluvox" - that makes me think of "luvox". Hmmmm. I wonder how that's working