Initial clinical studies

Phase II. Initial clinical studies for therapeutic safety and efficacy are performed in volunteer patients who are suffering from the disease for which the dmg has therapeutic promise. Recognition of toxic symptoms and side effects are vital at this point because these may occur here, even when not observed in animal studies or in Phase I. 

Test Article Specifications. In general, the product that is used in the definitive pharmacology and toxicology studies should be comparable to the product proposed for the initial clinical studies. 

While one may insert such terms in a study report, and CROs may accept such descriptions, it should be noted that the FDA and other regulatory agencies expect that the definitive safety studies be conducted with test article that is comparable to the product proposed for the initial clinical studies. Any differences, compliance (GMP/nonGMP) or other (manufacturing methods, product attributes), must be justified within the relevant regulatory submissions (e.g., IND or BLA/CTD). 

Safety concerns may arise from the presence of impurities or contaminants. It is preferable to rely on purification processes to remove impurities and contaminants rather than to establish a preclinical testing program for their qualification. In all cases, the product should be sufficiently characterized to allow an appropriate design of preclinical safety studies. In general, the product that is used in the definitive pharmacology and toxicology studies should be comparable to the product proposed for the initial clinical studies. (ICH S6)... 

Mishell, D. R., Jr., Lumkin, M., and Jackanicz, T. (1975), Initial clinical studies of intravaginal rings containing norethindrone and norgestrel, Contraception, 12, 253-260. 

Griffin TW, Brill AB, Stevens S, Collins JA, Bokhari F, Bushe H, Stochl MC, Gionet M, Rusckowski M, Stroupe SD, et al Initial clinical study of indium-lll-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer. J Clin Oncol 1991 9(4) 631-40. 

Should a candidate demonstrate positive effects in Phase I trials, then Phase II trials (initial clinical study for treatment efficacy and continued study of safety) are... 

Phase I studies involve some combination of the evaluation of initial safety and tolerability, pharmacokinetics, pharmacodynamics, and an early measurement of drug activity. The initial clinical study is typically a single dose study conducted in normal healthy volunteers. The initial dose in the study is estimated from the nonclinical data and this dose is escalated until adverse events are seen. This study results in the determination of the maximally tolerated dose of the drug. Analysis of pharmacokinetic parameters and relation of blood levels to adverse events gives great insight for future studies. 

The initial clinical studies served as the first indication that Hansen s disease could be treated by means of a specific antibacterial agent. Up to then, leprosy had for centuries been regarded as incurable. 

Initial clinical studies employing a STAT-1 decoy ODN in allergic asthma as well as psoriasis have been performed by AVONTEC GmbH. No side effects were seen in these early Phase I trials, and the compound was well tolerated. 

Modulation of Pgp activity is considered a potential approach to reverse MDR and improve therapeutic outcomes in cancer patients. Initial clinical studies with Pgp inhibitors such as verapamil and cyclosporin showed modest success in reversing resistance in a small number of patients, but significant... 

R.M. Szeimies, S. Karrer, A. Sauerwald, M. Landthaler (1996). Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses an initial clinical study. Dermatology, 192, 246-251. 

The initial clinical studies of GW veterans were largely negative, and no pathology could be detected using routine physical examinations and diagno.stic tests (Bourdette et al., 2001 Fukada et ai, 1998 Haley et al., 1997). However, in recent years Haley and others have begun to integrate... 

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