|2005D-0122||Guidance for Industry on Exploratory IND Studies|
|FDA Comment Number :||EC1|
|Submitter :||Mr. Gary Aronson||Date & Time:||05/04/2005 06:05:47|
|Organization :||Targa Therapeutics Corp.|
|Category :||Drug Industry|
| Targa Therapeutics Corp.
3960 W. Point Loma Blvd. Suite H - PMB 198
San Diego CA 92110
Tel.: 1-858-488-1288 Fax: 1-858-488-6288
Dockets Management Branch (HFA-305)
Food and Drug Administration
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Rockville, MD 20852
April 28, 2005
Docket No. 2005D-0122
Draft Guidance for Industry on Exploratory Investigational New
Drugs Studies; Availability
Docket No. 2005D-0122
I agree with the overall thrust of this document and its intent to make exploratory IND's less cumbersome and expensive. Some of the specific language needs to be altered to accomplish this goal. In particular, the calculation of the stopping dose in escalating studies is problematic:
?The results from the preclinical program may be used to select starting and maximum doses for the clinical trials?The maximum clinical dose would be the lowest of the following: (1) ? of the 2-week NOAEL; (2) ? of the AUC at the NOAEL in the 2-week rodent study, or the AUC in the dog at the rat NOAEL, whichever is lower; or (3) the dose that produces a pharmacological response or at which target modulation is observed in the clinical trial. Escalation from the proposed stopping dose should only be performed after consultation with and concurrence of the FDA.?
After stating that animal studies are not predictive of results in humans, this rigid, animal-based mathematical formula is inappropriate. It is not
| supported by any scientific data and it ignores substantial differences between drugs and amongst the severity and type of indications being treated. It is likely to have the effect of inhibiting the gathering of useful clinical data on efficacy and dose-response relationships, without adding any significant protection to human subjects.
Instead of using this artificial standard based on inappropriate animal models, the stopping dose in dose-escalating trials should be based on the actual incidence and severity of adverse events in humans in each trial.
Moreover, a balancing of the seriousness of each adverse event with the potential clinical benefit should be made. For example, in the case of clinical trials involving cytotoxic agents (which are well-known to have significant incidence of side effects) and seriously ill or terminal cancer patients who have no good clinical alternatives, a higher tolerance for adverse events should be permitted.
Thank you very much.
Gary Aronson, CEO
Targa Therapeutics Corp.