states extended release not widely used? never heard that before.

http://www.bloomberg.com/news/2013-0...on-s-drug.html

The medication would likely be used most among patients for whom the standard medicines, levodopa and carbidopa, have stopped working as reliably, said David Amsellem, an analyst with Piper Jaffray & Co. in New York. Rytary could generate peak sales of $200 million to $300 million, Amsellem said.

“A controlled-release product is something that has been elusive over the years,” Amsellem said in a telephone interview.

Impax, which specializes in controlled-release drugs, will develop and sell Rytary in the U.S. and Taiwan while GlaxoSmithKline Plc (GSK), based in London, will market it in other regions throughout the world. Impax already markets a generic version of a longer-acting combination called Sinemet, sold by Merck & Co. (MRK)

Merck’s Sinemet extended-release carbidopa-levodopa tablet received approval in 1991 though it’s not widely used, Amsellem said. People who use it are more likely to suffer impairment of voluntary movement than those who use the immediate-release version, according to the label for the medication.
Involuntary Movements

Patients with advanced Parkinson’s disease who used Rytary experienced a 34 percent decrease in the amount of time during waking hours when the medication wore off and involuntary muscle movements returned, the companies said in an August 2011 statement. This was compared with a decrease of 10 percent for those who used the immediate-release generic drugs combined with entacapone, a medicine that helps more of the other treatments reach the brain.

This is just anecdotal but I had one neuro prescribe Sinemet CR for me after cautioning me that she did not recommend it because not reliable. My new neurologist said I might get a 1/2 hour of more on time but unpredictable. My experience with CR mirrors their observations. At first I had a minor benefit, but then ended up with a build up response where I would take CR and it did not do anything but at around 3-4 in the afternoon, I would end up with wicked dyskinesia.

However, the article here states that a "re-inspection of a plant involved in the development..." was required. Impax was warned in a 2011 letter. This sounds like a quality control or manufacturing process issue rather than statistical significance for efficacy. Doesn't it?

Laura

IMPAX has had production problems on other drugs, I assume it will be approved.
Hopefully it will be better than CR and insurance will pay for it.

I use CR, but agree it is unpredictable but I only take sinemet and at low enough levels that is doesn't build up, I seem to have the opposite affect in that at times it doesn't seem to be working later in the day. i'll take 50mg IR/200mg CR first thing in the morning, then follow that up with 100mg when i start to wear off, maybe 3 hrs later, with a 200mgCR. Certainly not the smoothest outcome, I'll sometimes add another 50mg or split a 200mgCR but it works well enough.

After testing various combinations of instant release and controlled release generic Sinemet to optimize control of my PD symptoms, my MDS and I have settled on a regimen of one 25/100 IR along with one 50/200 CR every 3.5-4 hr throughout the day. If I begin meds at 7 AM, four rounds of this combination carries me through until bedtime at 10-11 PM.

The total daily DOPA is a whopping 1200mg. However the available DOPA from the CR is only 50-60%, so effective daily DOPA is less than 900mg.
The rationale for this regimen was to provide a rapid rise of DOPA from the IR, accompanied by the maintenance of a "floor level" in the therapeutic range by the CR.

I am the original low-dose dextromethorphan "white rat", religiously taking 3-4mg of the drug in the form of OTC pediatric preparations of cough syrup at bedtime since 2005. I attribute the slow progression of my PD symptoms to the DXM.

My PD is of the rigid-bradykinetic type (no significant tremor), and I have only mild dyskinesia (so far). My Dx was made in April 2001, almost 12 years ago.

Robert

The link below gives details of the FDA's inspection of Impax Laboratories on dates between 8th January and 22nd January, with a report dated 28th February 2013.

http://www.fda.gov/downloads/AboutFD.../UCM345866.pdf

There are 12 observations. The first two are:

"The accuracy, sensitivity, specificity, and reproducibility of test methods have not been established."

"Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product."

Observation 12 states:

"Employees engaged in the manufacture and processing of a drug product lack the training and experience required to perform their assigned functions."

Details of how these apply to Levodopa/Carbidopa IPX066 are given.

Since then GSK have issued a press release:

http://www.gsk.com/media/press-relea...ir-collab.html

"GlaxoSmithKline and Impax Pharmaceuticals terminate their collaboration on IPX066

Issued: Monday 29 April 2013, London UK

GlaxoSmithKline (GSK) plc and Impax Pharmaceuticals today announced that they are terminating their collaboration for the development and commercialisation of IPX066 outside the United States and Taiwan. IPX066 is a carbidopa-levodopa extended release product in Phase III development for the symptomatic treatment of Parkinson’s disease and is not approved anywhere in the world.

Under the terms of the agreement entered into in December 2010, GSK’s right to develop and commercialise IPX066 outside the United States and Taiwan will transfer back to Impax with effect at the end of July 2013. The decision has been reached because of delays in the anticipated regulatory approval and launch dates in countries in which GSK has rights to commercialise the product."

John