Clinical Trials

like many others I am keeping a watch for new developments in treating hep c, such as BILN 2061.  I frequently read that drugs are at stage 2 of the clincical trials procedure (such as biln) or at stage 1.  
Does anybody know what this means? What are the various stages? What happens at each stage and how long from stage 2 to being generally available? I'm talking generally, not just about Biln.

[BobK]

Phase I trials use a very small number of people to evaluate how the drug is tolerated...usually healthy disease free folks are used but with HCV drugs infected people suffice...provided they have no complications...eg decompensated cirrhosis.  Typical numbers are often less than 100 and more often less than 50.

Phase II trails are directed at a larger number of patients and are used to determine efficacy of the therapy. Patient numbers are around the 100's

Phase III trials utilize a fairly large number of patients (often 1000 or more)and are used to try and find out the frequency of adverse events associated with the drug(s)as well as refine the efficacy of the treatment.

All in all these trials take many years to complete, 5-10 is not uncommon.  From Phase III trials to general availability may take an additional 2-4 years while the data is being compiled and reviewed.  

Given the relatively small number of people involved in testing these drugs it is not suprising to find out that more than 50% of both adverse and desirable effects of a drug are not discovered until the drug is released for use in the general population. It is impossible to test a drug for all possible side effects prior to release...well maybe not impossible but the time frame (and $$) needed would make it prohibitive to try to do so.

good luck,
BobK

ps: http://www.clinicaltrials.gov is a good starting place when looking for a trial to participate in.

[lackalustre]

I seems there are always lots of rumors going around about new drugs.  ive heard that protease inhibitors are a big flop, and  earlier i heard they cause heart problems and trials were stopped.  then i heard that was wrong.  if they are in trials then information can leak out but its not supposed to.  
   it would be good to get some solid information about BILN or protease inhibitors on an up to date basis.  we all need hope for this disease and a CURE thats non toxic.

[Steve']

Hi there not related to your drug but I just thought I'd tell you guys & girls I'm on week #10 a clinical trial right now with "Roche" I'm in Sydney, Australia ... Pegasys Riba combo. Bye For Now... Keep Focused

[BobK]

Clinics in Liver Disease
Volume 7

[jonihs]

If you are a 2 or 3, see my post under treatment for relapsers thread.  Best wishes,  Joni

[BobK]

Substrate analogues
Landro and coworkers [86] were the first to report peptide-based inhibitors of the NS3-4A proteinase. In substrate specificity studies, these authors have identified P1′ substitutions with the amino acids proline, tetrahydroisoquinoline-3-carboxylic acid (Tic) or pipecolinic acid (Pip), respectively, that abolished cleavage but retained a high affinity of the corresponding peptides for the proteinase. The decapeptide Glu-Asp-Val-Val-Leu-Cys-Tic-Nle-Ser-Tyr was reported to be a potent, competitive inhibitor of the NS3-4A proteinase. Recently, Ingallinella et al further explored the residues corresponding with the P′ portion of the noncleavable substrate analogues in order to optimize binding to the substrate binding cleft [87] . Their effort led to a substrate-derived peptide inhibitor of the NS3-4A proteinase with the amino acid sequence Asp-(D)Glu-Leu-Ile-Cha-Cys-Pro-Cha-Asp-Leu. This peptide displayed a more than three orders of magnitude increase in potency relative to the starting peptide. Although a great deal of selectivity and potency can be obtained through the design of substrate analogues, their peptidic nature and relatively large molecular weight limits cell-membrane permeability and bioavailability, thus preventing their employment in clinical trials.

Serine-trap inhibitors
Serine proteinase inhibitors can typically be developed by derivation of the known substrate by replacing the scissile amide bond with an electrophilic

[newb]

This complete article can be viewed at: http://www.natap.org/2003/sept/092403_1.htm

Schering-Plough to Initiate First Head-to-Head Study Of Leading Hepatitis C Therapies

[sonata1]

Yes I found out about this today because I was contacted to  consider this trial.  Additionally I was told that the battle between Schering Plough & Roche now includes a third contender Infergen, concensus interferon (sp??)  So the trial will be a three-way - not a blind study - obviously if you were on Pegintron, you will now get Pegasys and the other way around.  You can tell if you are getting the infergen because it is 2X injected - oh yes, each one is accompanied by the wonderfully mellow drug of ribavirin.

I was also told that Schering Plough lost a lot of money when Pegasys came out, thus the trial to achieve some sort of statistics.

Of course this will benefit many.

[susan400]

I appreciate you all for posting these studies on the boards, but honestly, I can't read them.  My attention span is such that it's just too long and involved for me to stay on track.  As far as Infergen goes, it's not a new drug, it's been around for years.  I was on it about 3 years ago.  It's not the cure-all that some people are claiming.  Unless you stay on daily doses, it really doesn't do all that much more than the other interferon preparations.  I was on high dose daily doses of Infergen for about 6 weeks and then, was cut back to 3 times a week.  Never got a remission.   Susan400

[merryBe]

thanks for posting this Bob. I am already in diebetic (diabetic) territory due to growth hormone therapy for low pituitary function. And I start Interferon next week. there's a lot to digest here,

question:

Do you think the glyset, for it iminosugar would be a good choice to add to my regeme?
I'm not currently on anything, due to liver, and sulfa concerns. This looks like I could both slow absortion without harming the liver, and possibly boost my HCV response. Am I reading this right?
(not a physician) My doc wants to put me on Byetta, but I'm concerned about that causing nausea, as does the INF, plus, I don't want to cause malnourishment which tx for HCV may cause enough of.