Posted On: 08/30/2013 8:35:44 PM
Post# of 72440
I was just reading yesterday, when looking at wet amd race, about the advances made in direct ophthalmic drug delivery (none of which are effective enough yet for amd because it is so hard to reach rear structures of eye with high enough dose of direct ocular administrated drug). Fascinating stuff. This (http://www.retinalphysician.com/articleviewer.aspx?articleID=107657)inta-arterial catheter administration is the treatment I am most familiar with for RB and warning to all that the pictures are disturbing. It would be a great thing to have noninvasive treatment.
If ctix chooses the cup or intra-arterial delivery method - I would think they'd have to start from scratch with early phI. They said in their pr re RB that they would start with phII once adult mtd established. That seems a little optimistic given the fact that this current safety trial would then have totally different pk parameters than a direct ocular administration would.
If same route of admin, the NIH guidance (in Handbook for Cancer Drug Development, c2004) for pediatric trial is: "Phase I studies in children are generally performed after an adult MTD has been established, and dose-escalation begins at 80% of the adult dose, to minimize under-treatment."
And here,(http://mct.aacrjournals.org/content/5/8/1905.full) author says basically the same thing: "Although the progress of pediatric drug development is delayed while awaiting initial adult clinical trial results, this carries some advantages. By the time pediatricians are conducting a phase I trial, adult data on toxicity is available. Dose escalation can then be based on the adult MTD. Because children tolerate toxicity better than adults, the pediatric MTD is rarely less than the adult MTD. Typically, the initial dose level in a pediatric phase I will be 80% of the adult MTD and the dose will escalate from there. This helps limit both the total number of patients needed to complete a pediatric phase I trial as well as the number of patients treated at lower, often subtherapeutic doses. Additionally, adult trials provide preliminary efficacy data. This can help in prioritizing which drugs to bring into pediatric trials. While care must be taken when extrapolating efficacy data from adult studies to pediatrics, doing so can provide useful information beyond preclinical models."
Now, if you think the administration of K might be direct to eye - I have no idea at all how they'd estimate start dose. Novel drug and novel technology? Would they take on so much?
If ctix chooses the cup or intra-arterial delivery method - I would think they'd have to start from scratch with early phI. They said in their pr re RB that they would start with phII once adult mtd established. That seems a little optimistic given the fact that this current safety trial would then have totally different pk parameters than a direct ocular administration would.
If same route of admin, the NIH guidance (in Handbook for Cancer Drug Development, c2004) for pediatric trial is: "Phase I studies in children are generally performed after an adult MTD has been established, and dose-escalation begins at 80% of the adult dose, to minimize under-treatment."
And here,(http://mct.aacrjournals.org/content/5/8/1905.full) author says basically the same thing: "Although the progress of pediatric drug development is delayed while awaiting initial adult clinical trial results, this carries some advantages. By the time pediatricians are conducting a phase I trial, adult data on toxicity is available. Dose escalation can then be based on the adult MTD. Because children tolerate toxicity better than adults, the pediatric MTD is rarely less than the adult MTD. Typically, the initial dose level in a pediatric phase I will be 80% of the adult MTD and the dose will escalate from there. This helps limit both the total number of patients needed to complete a pediatric phase I trial as well as the number of patients treated at lower, often subtherapeutic doses. Additionally, adult trials provide preliminary efficacy data. This can help in prioritizing which drugs to bring into pediatric trials. While care must be taken when extrapolating efficacy data from adult studies to pediatrics, doing so can provide useful information beyond preclinical models."
Now, if you think the administration of K might be direct to eye - I have no idea at all how they'd estimate start dose. Novel drug and novel technology? Would they take on so much?
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