United clinical trial

Human growth hormone, used as a human pharmaceutical, is approved for only one indication in the United States, treatment of growth failure owing to hGH deficiency, a condition known as pituitary dwarfism. However, clinical trials are under way to test its efficacy in Turner s syndrome, bums, wound healing, cachexia, osteoporosis, constitutional growth delay, aging, malnutrition, and obesity. 

Turner s Syndrome. Turner s syndrome is a genetic disorder of females characterized by short stature, nonfunctioning ovaries, and failure to develop secondary sexual characteristics. Several clinical trials in the United States, Europe, and Japan have demonstrated that hGH can accelerate... 

Acetyl-i-carnitine (4) is marketed in Italy for dementia as of this writing it is also in Phase III clinical trials in the United States and Europe. In a double-blind, placebo-controUed clinical trial over a one-year period involving 130 patients with clinically diagnosed AD, a slower rate of deterioration in 13 of the 14 outcome measures was observed in the dmg-treated group (28). Earfler smaller scale pilot studies in demented patients had also shown some improvement of various behavioral and cognitive functions (29). 

Influenza. Although current influenza vaccine (subunit spHt vaccine) has been in use yearly for the elderly, it is not recommended for the general population or infants. Improvements to increase or prolong the immunogenicity, reduce the side-effects (due to egg production procedure), and provide mass protection are stiU being pursued. One approach is to use a five, attenuated vims though cold adaptation. A vaccine has been used in Russia and demonstrated to be safe and efficacious for infants (82). Clinical trials for a similar vaccine are being carried out in the United States (83). 

Pepiomycin is marketed in Japan and was in clinical trials in the United States in 1990 lihlomycin is at an early stage of development. Others include taHysomycin A [65057-90-1J, reported in 1977, which was in clinical development at one time (240), and phleomycin [11006-33-0], reported in 1956 (241), which was too toxic for dmg use. 

Fibric Acid Derivatives. Fibtic acid derivatives have been used since the 1960s for control of blood Upid levels. The four most well-known compounds in this class ate fenofibrate, gemfibrozil, clofibrate, and bezafibrate, shown in Table 5. Fenofibrate has been the most popular fibtic acid derivative in Europe, and has mote tecentiy been investigated extensively in clinical trials in the United States (153). Bezafibrate is stmcturaHy related to clofibrate, and has tecentiy been reviewed by Western European and AustraUan clinical trials (154). 

Approaches to cytotoxic chemotherapy iaclude special emphasis on dmg targeting and toxicity alleviation. The directions ia which new dmg discovery strategies are moving and the criteria used for advanciag compounds iato clinical trials (2) are discussed hereia, as are all of the dmgs approved by the United States Food and Dmg Administration (FDA) for the treatment of cancer as of this writing and those compounds ia clinical trials. 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

The imidazoline denvative cibeiuoline (64) is a class I antiarrhythmic agent which has undergone clinical trials in the United States with apparently satisfactory results It is synthesized by diphenylcyclopropananon of acrylonitrile by thermal carbene generation from diphenyldiazo methane (62) to give 1 cyano 2,2 diphenylc>clopropane (63) Reaction of this with ethylenedia mine tosylate completes the synthesis of ciben/oline (64) [221... 

This section will review the phase III clinical trials of IV thrombolytic agents for acute ischemic stroke, organized by the type of agent and the time window from stroke onset to study drug delivery (Table 3.1). The 1995 National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial is presented first because it showed that IV rt-PA, given within 3 hours of stroke onset, reduced stroke-related disability. This trial was the basis for the United States Food and Drug Administration (FDA) approval for rt-PA for use in acute ischemic stroke. 

LT4 is indicated for patients with overt hypothyroidism.22 However, the need for treatment is controversial in patients with mild or subclinical disease (TSH less than 10 milli-units/L). There are no large clinical trials that show an outcome benefit with treating these patients, and the therapeutic decision must be individualized.1,23 Many patients with subclinical hypothyroidism do, in fact, have subtle symptoms that improve with LT4 replacement. If the patient s serum cholesterol is elevated,24 or if serum anti-TPOAbs are present, many clinicians recommend LT4 therapy. 

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