Antipsychotic Drug Stabilization Period For Long-Term Studies Can Be Short, Vanda Pharma Says
[Some information about what Vanda is up to].
The patient response stabilization period for long-term studies of antipsychotic drugs prior to relapse prevention studies should be relatively short, Vanda Pharmaceuticals said.
“Lengthy stability periods preceding the withdrawal phase of long-term maintenance studies do not reflect current clinical practice,” Vanda’s briefing materials for the Oct. 25-26 meeting of FDA’s Psychopharmacologic Drugs Advisory Committee maintain.
“Introduction of lengthy stability periods (=6 months) would not be expected to contribute to the clinical meaningfullness of such studies,” Vanda said.
The committee will discuss trial designs for the long-term efficacy of psychiatric drugs.
Vanda Pharmaceuticals took over the development of the antipsychotic iloperidone from Titan Pharmaceuticals and Novartis in June. Titan out-licensed iloperidone to Vanda after a six-week trial showed QTc interval prolongation with the product.
Vanda was founded in 2003 by former Novartis Worldwide Pharmaceuticals CEO Jerry Karabelas and former Novartis VP-Pharmacogenetics Mihael Polymeropoulos.
FDA has suggested that patients on chronic psychiatric medications need to be in responder status for a longer period of time prior to relapse prevention studies.
“We have indicated that patients need to be in responder status for at least six months prior to randomization in a randomized withdrawal trial,” FDA’s briefing documents for the meeting state.
“This proposed policy has been met with considerable resistance and question and for this reason, we thought it would be useful to bring this general issue to the committee for discussion,” FDA added.
Vanda pointed to the recently released results of the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study as support for its thesis on duration of stabilization.
The average time patients responded to antipsychotic treatment was one month, Vanda pointed out. “Thus in standard clinical practice, the mean duration of stabilization is relatively short.”
“Stabilization periods that precede randomization to the withdrawal portion of a long-term effectiveness trial should not exceed the expected duration of successful management of schizophrenic symptoms.”
Vanda also argues that active control studies are appropriate for long-term antipsychotic efficacy trials.
FDA has expressed concerns that such trials lack the sensitivity to detect treatment differences, in part because it is difficult to discern whether the active control would have separated from placebo.
The company looked at six long-term antipsychotic trials and found the mean difference in relapse rates for active treatments vs. placebo to be 40% for 12-month trials and 27% for six-month trials.
“These data support the conclusion that in long-term recurrence prevention studies, antipsychotics separate consistently from placebo,” Vanda concluded.
In addition, based on the studies, “it can be concluded that a margin of separation between active and test drug in an active-control trials must be at least <27%,” Vanda noted.
FDA will ask the committee first to deliberate on longer-term studies for drugs for major depressive disorder and then whether their conclusions extend to other chronic psychiatric illness drug categories.
To watch a webcast of this meeting, click on the button below. To arrange for live videoconferencing or to order videotapes & DVDs, email FDATV@elsevier.com or call 800-627-8171.
Posted: Friday, October 21, 2005 |
