# Novel Drug Shows Strongly Positive Results in Irritable Bowel Syndrome With Constipation



## SpAsMaN* (May 11, 2002)

Novel Drug Shows Strongly Positive Results in Irritable Bowel Syndrome With Constipation;May 25, 2007 (Washington) — A novel, first-in-class guanylate cyclase-C (GC-C) agonist, linaclotide acetate (Microbia Inc, Cambridge, MA), exhibited markedly positive results in a phase 2a study of patients with irritable bowel syndrome with constipation (IBS-C). IBS-C accounts for 40% of cases of IBS. Linaclotide's activation of GC-C, a transmembrane protein located in the gut epithelium, causes an increase in intestinal fluid secretion and inhibits colonic fluid absorption. Patients receiving the drug showed a strong dose-response, with a significant acceleration in gut transit time, resulting in more frequent stools with a softer consistency. The study was conducted by Viola Andresen, MD, of the Department of Health Sciences Research in the Division of Biostatistics, and colleagues at the Mayo Clinic in Rochester, Minnesota. Results were reported here at Digestive Disease Week 2007.The study involved 36 women with IBS-C randomized to linaclotide 100 or 1000 µg daily or placebo for 5 days. The treatment period was preceded by a 5-day baseline observation period.Gastrointestinal transit time was measured by scintigraphy, and bowel function was recorded daily using the Bristol Stool Form Scale.There was a strong dose-response effect on colonic transit time within 48 hours with linaclotide. Stool frequency, consistency, time to first bowel movement, and ease of passage all improved significantly with the higher dose (P < .001), an indication of some pain relief. Dr. Andresen commented that ease of passage implies a decrease in pain, which is one of the most significant issues in IBS-C.Ascending colon transit time was significantly accelerated (P = .004) and overall colonic transit time increased significantly (P = .020), with the higher dose of linaclotide compared with placebo (P = .010).There were no safety issues with linaclotide. Dr. Andresen pointed out that linaclotide's effects are local, confined to the intestinal epithelium, and are not systemic. There were no effects on the upper gastrointestinal system."There is definitely a need for new treatments for IBS," Dr. Andresen told meeting attendees. "These results were quite exciting. We now need more clinical trials with more end points." Linaclotide is also under development as a treatment for chronic constipation.Microbia announced that based on these positive phase 2a results, designed primarily to assess the safety of linaclotide, a phase 2b study is now underway, involving 300 patients with chronic constipation.Maria Abreu, MD, director of the Inflammatory Bowel Disease Center and associate professor of medicine at Mount Sinai School of Medicine in New York City, moderated the panel at which Dr. Andresen announced her results. She echoed Dr. Andresen's words, saying "IBS has few good therapies and patients have a lot of pain.... This study shows promising progress."Dr. Andresen reports no relevant financial relationships. Dr. Abreu serves as an advisor to Procter & Gamble, Abbott, UCB, Schering, and Berlex, none of which were relevant to this study.DDW is jointly sponsored by 4 societies: the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).DDW 2007: Abstract 532. Presented May 21, 2007.


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## annie7 (Aug 16, 2002)

yeah i read this too today on medscape but to me it was a little disappointing because to me it sounds that this drug is kind of like amitiza because, like amitiza, it increases the amount of fluid in the intestines. and yes, it does say that gut transit time was accelerated due to the increase of intestinal fluid but the amitiza info claimed that too. i've found i need more than intestinal fluid increase--i need the peristalic push to make it all come out--so amitiza didn't help me but zelnorm does because it increases motility and gives me that push--moistening stool alone doesn't help. so i'm looking for something that works like zelnorm. although of course i'll definitely try this new drug if it makes it through the trials--i'll try anything. or maybe i'm mistaken and not interpreting all this info on mechanism of action correctly--experts and others opinions welcome! it would be great to find a replacement for zelnorm.


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## 16430 (Oct 30, 2006)

Annie7. You summed my problem very accurately. I have exactly the same issue of needing a persitaltic push rather than making it more liquid.


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## lorilou (May 9, 2003)

me too- peristalisis is what its all about for me.any one considered going herbal and seeing what herbs help motility? they scare me thoughas the side effects can just about kill you...maybe we should begin a research party to see what we can find.God blessLori


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## fizzixgal (Apr 6, 2007)

Annie7, you expressed my thoughts on this report exactly. Of course I would try this drug if it came to market, but yes it sounds a lot like Amitiza in an important way. So far the only new drug I've heard about that might replace Zelnorm is renzapride. My fingers are crossed for that one.


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## annie7 (Aug 16, 2002)

thanks everyone for your input. yes--renzapride!! can't wait! it really sounds promising. i was reading about it on alizyme's web page and they expect the results of the US Phase III clinical trial for renzepride for IBS-C to be available early in 2008. i wonder how long it will take from there to (hopefully!!!) an approval...and hopefully we'll get zelnorm back too although who knows how long that will take. http://www.alizyme.com/alizyme/products/renzapride


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## Joan Mack (May 20, 2007)

hi everybody. I would probably not do well on this drug. Miralax is supposed to add water to your stools too and it just about killed me. I never had IBS so bad! I too need the push of zelnorm. My gi doc said there is nothing like zelnorm out there but we were talking about him giving me a script. Hopefully there is something out there coming in the future. But how long do we have to wait and will they ever reinstate zelnorm?







I think all we can do is pray at this point!


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## GailSusan (Dec 23, 2000)

I have the same issue. Miralax and similar treatments just make me feel bloated and miserable. I need strong hot coffee and my Zelnorm on an empty stomach each morning to have a BM.


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## libraryg (Jun 20, 2007)

Hi all, new member here. I too was on Zelnorm, and it worked very well for me. I have had IBS-C for over a dozen years, and since last summer it has steadily worsened.I am in the clinical study trials for Microbia's linaclotide, and have been for a few weeks. While it does not produce quite as regular the results as Zelnorm, it has performed very well for me overall. This is a double-blind study: neither I nor the clinician handling my case knows the dosage I am on, or if it's a placebo. There are 4 different dosages, and I know I am on "the real thing" by the results I have seen. I have had to phone Microbia daily to answer many automated questions regarding my bowel movements, which is a small price to pay for relief! I am very sad to say that the study ends this week, and after that I truly don't know what I will do. I had the good fortune to have my Zelnorm 'script refilled (60 tabs at 6 mg), literally the day before Novartis pulled it. **whew!** Since I have not taken it since before the study began, I have the whole bottle left to baby along for a few weeks.....but then?I have had no ill effects whatsoever from the linaclotide. No nausea, unlike Amitzia, which I have not tried and am deeply leery of. I am glad to have found this board and look forward to sharing with and learning from you all!Lisa


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## lorilou (May 9, 2003)

library,do you have any clue as to when this new drug will be out for the public?keep us posted on how its going for yaLori


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## libraryg (Jun 20, 2007)

lorilou said:


> library,do you have any clue as to when this new drug will be out for the public?keep us posted on how its going for yaLori


From what I understand, if the FDA gives it the go ahead, we are looking at a 12 to 18 month wait. Could be shorter or longer, tho...........hoping for the shorter wait myself!I also hear that there is a "good chance" that Zelnorm will be back on the market, maybe even by the end of the year. Wouldn't that be grand?


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## Dawhna (Oct 17, 2004)

Gosh, I can really relate to you all. I've been a member here but not posted much until lately...not really sure if I truly had IBS. Reading all your posts convinces me I do. I have the propulsion problem too. And then, to top it off, if I get loose stools, I don't have a very tight sphincter and that, as you can guess, leads to some embarrassing moments! No doctors seem to be able to help me. For years when I was taking a certain form of calcium...hydroxyapitite (sp), I had sudden squirty diarrhea and then came to realize it was the magnesium in the supplement. Once I stopped that I reverted back to my life long plague of constipation. I had hemorrhoid surgery when I was 19 and gave birth to 4 babies, vaginally, so my perineium and rectum could be weakened from all that.It's just such a bummer. Why can't I poop like other people? My husband has a hard time understanding my situation since he poops several times a day normally.It's just a darned poopy problem to me. I never took Zelnorm but wish I had. It totally sounds like what would have helped me!!! I hate being so consumed by bathroom talk and long to function like 'everyone else.'


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## Bab (Jul 10, 2007)

I finished my last Zelnorm last week. I was ok for a couple of days, then spent another few in AGONY!! I am going to go to Mexico and see if I can find it over there. Damn the lawyers and their constant lawsuits. They have these drug companies running scared.


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## Mary5 (Apr 17, 2006)

Librayq, how exciting to be participating in the trial for the new Microbia medication! Especially if it is working and without major side effects! Please keep us posted.GailS,Lorilou,Annie7,Ramana, I am on my second or third attempt with the Amitiza, to which I came back after trying FruitEze, and then OTC laxatives (that I hate to take). Amitiza increases fluid secretions in the small intestine. Possible side effects are diarrea, headache and nausea. It works for me to a certain extent, it is peristaltic and I go but it tends to be rather watery and I do feel a little sick. Also, it still does not or hasn't for me produced a regular bowel movement. Maybe it is because I eat so little...Also, lots of gas that roams around the body and is very painful. I have an appointment with the gastro doctor first week of August to get his feedback on what else I can do or take to complement this. And yes, it is very expensive so I also want to ask him if I really need to take 2 a day, what has he found out in his practice since it came out etc. But so far it is the only thing out there.I wanted to tell you that I did go very well for quite a while with herbal teas with senna, Smooth Move was one. Senna is a stimulant laxative (Sennokot etc) and while it has been around forever and is relatively gentle within that category, I do understand that if you use it every day then your body will start requiring it to function. However, it works very well so you could try having a cup after dinner once or twice a week. Yesterday I asked the pharmacist if I could take Amitiza AND tea of senna. He said yes because they work with different parts of the GI tract. I asked him because although the Amitiza sent me running to the bathroom I still had/have backup in there including gas, and the corresponding bloating, pain etc. In fact I stayed home from work today to try and recover. So I may use it tonight and hopefully get rid of all in the morning. As you all know by now nothing seems to work on a long term basis...My goal is to find a natural or organic solution and not depend on any pill. I did write to Stonyfield yogurt for suggestions since even a spoonful of yogurt gives me the worst gases.Anyway good luck to all and let's continue the discussion.


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## SpAsMaN* (May 11, 2002)

Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome.http://www.medscape.com/medline/abstract/1...&src=nlbestclinical trials:http://www.clinicaltrials.gov/ct/show/NCT00460811?order=2


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## 13863 (Mar 23, 2007)

I have the Amitiza from my doctor to try but haven't started it yet. I am afraid of the nausea. Clinical study, I am wondering about one I saw on TV this week. How do you know if it is safe?I felt better on the Zelnorm most of the time anyways.


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## Joan Mack (May 20, 2007)

hi ... I will dance if zelnorm is brought back. there is no substitute.........I am very sad about the general state of things.............why can't we sign an acknowledgement that we realize and accept any risks. I sent a postal money order to oregon for $83 for zelnorm from mexico. I have enough for a while. If that order does not come through I am finished........................I don't blame the lawyers, I blame washington beauracrats.


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## libraryg (Jun 20, 2007)

I must say, between the Zelnorm and the linaclotide trial I was in, I would be more than happy to take either of these! Granted, I was only on the lina trial a few weeks, and who knows what the long term effectiveness may be?........I was on Zelnorm nearly 4 months and it worked extremely well. On the lina trial, I had to phone in to Microbia each day and give in depth info on my bm's.......if, when, how many, how much strain, consistency, etc......... they were looking for the "ideal" stool sample, which is sausage shaped, soft, smooth and regular, and easily passed, & well the linaclotide produced those for me on a shockingly (to me) regular basis! Zelnorm did fine by me in bowel evac, but the results were quite a bit more runny, and often of a certain consistant shade. Not that I am complaining......for a girl who is lucky on her own to poo twice a week, well a bm is a bm, and I will take whatever I can get, lol!!


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## libraryg (Jun 20, 2007)

Florida Girl, I too was fearful of nausea on Amitiza......but the only thing I found I had to fear was the horrific build up of stinky, gross to the max, gas and bloat!No nausea, no relief from IBS-C,but plenty of my smelling like, well.......ewwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww.......I do hope it works for you, sans the pukes!


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## Joan Mack (May 20, 2007)

I swear I'm gonna get a heart attack from all this FDA irritation. Zelnorm worked for years for me. I got very sick (had bowel cramp that literally bowed me over) with an attempt to clear up my problem. Following doctor's orders doesn't work. This cramp was so bad it caused my reflux to act up. If necessary I will use stool softeners...what can I say. I am very unhappy about it all. Is anybody listening to us?


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## inneedofhelp (Nov 23, 2007)

How were you able to be apart of the lina trial?


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