Clinical studies/trials pediatrics

In addition to antibiotics, dexamethasone has become a commonly used therapy for the treatment of pediatric meningitis. Corticosteroids inhibit the production of both TNF and IL-1. A series of clinical studies assessing the efficacy of corticosteroid therapy for the initial treatment of bacterial meningitis has reported conflicting results. " The majority of trials were conducted on small sample populations, each with different pathogenic bacterial causes and treatment modalities. The findings of several studies have shown significant... 

The FDAMA bill essentially codified and expanded several regulatory actions initiated by the FDA during the 1990s. Among the incentives offered by the bill, companies will be offered an additional six months of patent protection for performing pediatric studies (clinical trials) on already approved products. In fact, the FDA was mandated by FDAMA to develop a list of over 500 drugs for which additional information would produce benefits for pediatric patients. The FDA is supposed to provide a written request for pediatric studies to the manufacturers (Hart, 1999). 

Isocyanide-based MCR was also applied for the total synthesis studies of natural products containing piperazine substructure. For example, trabectedin (also known as ecteinascidin 743 or ET-743) is undergoing clinical trials for the treatment of breast, prostate, and pediatric sarcomas. Ecteinascidin 743 (2) is an extremely potent antitumor agent isolated from a marine tunicate, Ecteinascidia turbinate [12]. Eukuyama et al. developed the total synthesis of ecteinascidin 743 from a Ugi reaction [13]. The reaction of p-methoxyphenyl isocyanide 3 gave Ugi product 7, which was cyclized to DKP intermediate 8 (Scheme 1). 

As of the date of this chapter (circa March, 2002), labeling changes regarding pediatric use have resulted from only two programs—the study of buspirone in pediatric GAD and a pharmacokinetic study of fluvoxamine in pediatric OCD (fluvoxamine already had a controlled clinical trial in pediatric patients). Two placebo-controlled trials with buspirone in pediatric GAD did not reveal a treatment effect, and this negative outcome is reflected in Buspar labeling. A pharmacokinetic study of fluvoxamine dosed at 100 mg bid in pediatric... 

Three oral nucleoside analogs are licensed for the treatment of HSV and VZV infections acyclovir, valacyclovir, and famciclovir. They have similar mechanisms of action and similar indications for clinical use all are well tolerated. Acyclovir has been the most extensively studied it was licensed first and is the only one of the three that is available for intravenous use in the United States. Comparative trials have demonstrated similar efficacies of these three agents for the treatment of HSV but modest superiority of famciclovir and valacyclovir for the treatment of herpes zoster. Neither valacyclovir nor famciclovir has been fully evaluated in pediatric patients thus, neither is indicated for the treatment of varicella infection. 

Connor EM, Sperhng RS, Gelber R, Kiselev P, et al. 1994. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS clinical trials group protocol, 076 study group. NEJM. 331 1173-1180. 

ICH/M3 provides information about which studies -and of what duration - are needed before the different clinical phases of development can be started. In addition to this, timing of preclinical studies in dependence of clinical development plans, there are recommendations under which conditions different population can be included into clinical trials, populations such as men, women of childbearing potential or pregnant women and finally pediatric populations. 

Vitiello B, Davies M, Arnold LE, McDougle CJ, Aman M, McCracken JT, Scahill L, Tierney E, Posey DJ, Swiezy NB, Koenig K. Assessment of the integrity of study blindness in a pediatric clinical trial of risperidone. J Clin Psychopharmacol 2005 25 565-9. 

McIntosh K, Cooper E, Xu J, Mirochnick M, Lindsey J, Jacobus D, Mofenson L, Yogev R, Spector SA, Sullivan JL, Sacks H, Kovacs A, Nachman S, Sleasman J, Bonagura V, McNamara J. Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group. Pediatr Infect Dis J 1999 18(5) 432-9. 

Krogstad P, Lee S, Johnson G, Stanley K, McNamara J, Moye J, Jackson JB, Aguayo R, Dieudonne A, Khoury M, Mendez H, Nachman S, Wiznia A, Ballow A, Aweeka F, Rosenblatt HM, Perdue L, Frasia A, Jeremy R, Anderson M, Japour A, Fields C, Farnsworth A, Lewis R, Schnittman S, GigUotti M, Maldonaldo S, Lane B, Hernandez JE, et al. Pediatric AIDS Clinical Trials Group 377 Study Team. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nehinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. CUn Infect Dis 2002 34(7) 991-1001. 

Sperling RS, Shapiro DE, McSherry GD, Britto P, Cunningham BE, Culnane M, Coombs RW, Scott G, Van Dyke RB, Shearer WT, Jimenez E, Diaz C, Harrison DD, Delfraissy JF. Safety of the maternal-infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study. AIDS 1998 12(14) 1805-13. 

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