CDP323 Oral treatment in trials

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CDP323 Oral treatment in trials

Postby ewizabeth » Fri Apr 20, 2007 8:32 pm

Hi Everybody,

My neuro said I could have Tysabri, OR, he offered me the chance to be in one of two trials. The one he thinks I'd be good for is CDP323. I can't find any info on this, does anybody else know anything about it? Here is one link.

http://www.medicalnewstoday.com/medical ... wsid=17278

He said its mechanism is similar to Tysabri, but he thinks a daily pill will have a better safety profile, especially since a pill has a half life of a day, compared to a month for an infusion.

He thinks this has great promise... :? What do you all think?
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby Lyon » Fri Apr 20, 2007 9:52 pm

Hi Ewizabeth,
Dignan's got it in his phase II list and perhaps he knows more about it.

In a quick search I found this http://www.genengnews.com/news/bnitem.aspx?name=6408495 but it doesn't really give any specifics you could base a decision on.

I'll be gone until Sunday but if you haven't found anything by then I'll help you look.

It does say that it's an anti-inflammatory so in that regard it's not a vast departure from the "same old, same old" but if it proves safe and you can ditch the needles??

Bob
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Postby dignan » Fri Apr 20, 2007 11:44 pm

Here's an abstract from the 2006 ECTRIMS meeting. It reports on phase I results, which doesn't say anything about efficacy, just safety in the short-term.



Immunomodulation - Part I
Thursday, September 28, 2006, 15:30 - 17:00

Pharmacokinetic and pharmacodynamic properties of the VLA-4 inhibitor CDP323

M. Baker, A. Shock, T. Parton, P. Hales, G. Parker (Slough, UK)

Introduction: CDP323 is a small molecule inhibitor of vascular cell adhesion molecule 1 (VCAM) binding to alpha-4 integrin (VLA-4) in development for the treatment of immune system disorders including multiple sclerosis (MS).

Aims and methods: Three Phase I clinical studies were conducted in 75 healthy volunteers to investigate the pharmacokinetics (PK), safety and tolerability of CDP323 administered for up to 7 consecutive days. Ex-vivo inhibition of alpha-4/VCAM binding was utilized as a pharmacodynamic (PD) biomarker. An in vitro whole blood VCAM binding assay showed that the IC50 in human blood for CT7758, the active moiety of the prodrug CDP323, was 60 nM (95%CI 33-108). Study 1 evaluated 6 single ascending-dose levels, study 2 was a 7-day, multiple dose study of 3 dose levels, while study 3 was a male/female PK/PD comparison.

Results: CDP323 was well tolerated by human volunteers at oral doses up to 1000 mg bid for 7 consecutive days with an adverse event profile comparable to that observed with placebo. A PK model was developed to describe the disposition of CT7758 and an active metabolite, CT533652, which displayed linear kinetics over the doses investigated without gender effect. The PD effect closely followed the plasma concentration time course of the two active compounds and enabled the development of a PK/PD model that described the plasma concentration disposition of both compounds and directly linked these concentrations into an effect model without hysteresis. The IC50 value for the inhibition of VCAM binding derived for CT7758 (incorporating the pharmacodynamic contribution from the metabolite CT533652) from the PK/PD model in healthy volunteers was 63 nM, (95%CI 48-78), similar to that derived in vitro.

Conclusion: Oral administration of CDP323 resulted in the inhibition of VCAM binding in human volunteers. The development of a PK/PD model has assisted in the selection of dose regimen for evaluation in therapeutic clinical trials, providing evidence that the inhibition can be maintained throughout a 12 or 24 hour dose interval at dose levels well tolerated by human subjects.

http://www.akm.ch/ectrims2006/
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Postby ewizabeth » Sat Apr 21, 2007 6:34 pm

Lyon wrote:Hi Ewizabeth,
Dignan's got it in his phase II list and perhaps he knows more about it.

In a quick search I found this http://www.genengnews.com/news/bnitem.aspx?name=6408495 but it doesn't really give any specifics you could base a decision on.



Thanks Bob,

That's an excellent article. My neuro thinks this one has very good potential. Since Biogen is partnering with them, it must have the potential of being a widely used treatment. It seems pretty new though, so I don't know... :?:
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby ewizabeth » Sat Apr 21, 2007 6:37 pm

dignan wrote:Here's an abstract from the 2006 ECTRIMS meeting. It reports on phase I results, which doesn't say anything about efficacy, just safety in the short-term.



Immunomodulation - Part I
Thursday, September 28, 2006, 15:30 - 17:00

Pharmacokinetic and pharmacodynamic properties of the VLA-4 inhibitor CDP323

M. Baker, A. Shock, T. Parton, P. Hales, G. Parker (Slough, UK)

Introduction: CDP323 is a small molecule inhibitor of vascular cell adhesion molecule 1 (VCAM) binding to alpha-4 integrin (VLA-4) in development for the treatment of immune system disorders including multiple sclerosis (MS).

Aims and methods: Three Phase I clinical studies were conducted in 75 healthy volunteers to investigate the pharmacokinetics (PK), safety and tolerability of CDP323 administered for up to 7 consecutive days. Ex-vivo inhibition of alpha-4/VCAM binding was utilized as a pharmacodynamic (PD) biomarker. An in vitro whole blood VCAM binding assay showed that the IC50 in human blood for CT7758, the active moiety of the prodrug CDP323, was 60 nM (95%CI 33-108). Study 1 evaluated 6 single ascending-dose levels, study 2 was a 7-day, multiple dose study of 3 dose levels, while study 3 was a male/female PK/PD comparison.

Results: CDP323 was well tolerated by human volunteers at oral doses up to 1000 mg bid for 7 consecutive days with an adverse event profile comparable to that observed with placebo. A PK model was developed to describe the disposition of CT7758 and an active metabolite, CT533652, which displayed linear kinetics over the doses investigated without gender effect. The PD effect closely followed the plasma concentration time course of the two active compounds and enabled the development of a PK/PD model that described the plasma concentration disposition of both compounds and directly linked these concentrations into an effect model without hysteresis. The IC50 value for the inhibition of VCAM binding derived for CT7758 (incorporating the pharmacodynamic contribution from the metabolite CT533652) from the PK/PD model in healthy volunteers was 63 nM, (95%CI 48-78), similar to that derived in vitro.

Conclusion: Oral administration of CDP323 resulted in the inhibition of VCAM binding in human volunteers. The development of a PK/PD model has assisted in the selection of dose regimen for evaluation in therapeutic clinical trials, providing evidence that the inhibition can be maintained throughout a 12 or 24 hour dose interval at dose levels well tolerated by human subjects.

http://www.akm.ch/ectrims2006/


Thanks Dignan,

I wish I were technical enough to translate that... But thanks for the summary interpretation. I'll think about it. And if I go in for the sign up day, I'll get more information then, and if necessary pass on it as well.
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby connieb » Sat Apr 21, 2007 8:37 pm

Conclusion: Oral administration of CDP323 resulted in the inhibition of VCAM binding in human volunteers. The development of a PK/PD model has assisted in the selection of dose regimen for evaluation in therapeutic clinical trials, providing evidence that the inhibition can be maintained throughout a 12 or 24 hour dose interval at dose levels well tolerated by human subjects.

Sorry, I'm a little slow on the uptake-- but what does this drug actually do?
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Postby ewizabeth » Sat Apr 21, 2007 8:44 pm

Connie,

It has anti-inflammatory properties according to my neuro. He said the mechanism is similar to Tysabri, but in pill form. I hope I translated that correctly...
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby connieb » Tue Apr 24, 2007 6:59 am

Ty as a pill and without side effects wouldn't be a bad deal! Best of luck to you Ewizabeth-- keep us posted!
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Postby ewizabeth » Tue Apr 24, 2007 9:00 am

Thanks Connie, I will!

I should get a phone call from the coordinator within a few weeks. I'll check back here if and when I find out anything more about it.
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby Lyon » Tue Apr 24, 2007 5:35 pm

Hi Ewizabeth,
Hopefully you'll find the tail end of this webpage interesting IF YOU HAVE HIGH SPEED INTERNET
http://tinyurl.com/2jatyf
Bob
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Postby ewizabeth » Tue Apr 24, 2007 6:32 pm

Thanks Bob :D

That was a great article. Where do you find this stuff anyway?? That was very reassuring to read. Now I'm really excited about this treatment. It sounds just like my neuro described it! :)
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby Lyon » Tue Apr 24, 2007 6:40 pm

Ha! Nothing to it...other than spending WAY too much time on the internet!

I typed CDP323 into google, and if I remember correctly, it was within the first page of results.

A fast internet connection really helps to look and discount uninteresting prospects quickly.

I'll continue to keep an eye out!

Bob
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Postby scoobyjude » Tue Apr 24, 2007 6:58 pm

Sounds great Ewizabeth. Good luck!!!
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Postby ewizabeth » Tue Apr 24, 2007 7:03 pm

Thanks Scooby! :) I hope we get started soon!
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby CureOrBust » Wed Apr 25, 2007 3:54 am

connieb wrote:Ty as a pill and without side effects wouldn't be a bad deal! Best of luck to you Ewizabeth-- keep us posted!
I have a trial application info form for FTY720, and it compares the action to Tysabri (and its in a daily pill form)

They also hint at similar side effects, in that they will be paying special attention for those found in Tysabri (ie PML)
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