Clinical studies/trials

Adverse effects Extensive clinical trial studies for final products from oral or parenteral route Generally only known as a result of overexposure, accident, etc. 

Most clinical trials study voluntary patients who enter a research setting and are kept drug-free for 1 or more weeks. Severely disturbed patients, however, are usually not candidates for research. Because psychiatry lacks valid and reliable biological diagnostic tests, we do not know whether a given patient really has the disease under study. Further, some of the symptomatic volunteers who are often used in outpatient studies may not actually have the disease. 

To help protect the rights and welfare of volunteers and verify the quality and integrity of data submitted for review, the FDA performs inspections of clinical trial study sites and anyone involved in the research, says David A. Lepay, M.D., Ph.D., senior advisor for clinical science and director of the FDA s Good Clinical Practice Program. Lepay says that the quality of clinical trials has improved markedly since the agency started inspecting them back in 1977. 

Lebovitz HE, Dole JF, Patwardhan R, Rappaport EB, Freed MIRosiglitazone Clinical Trials Study Group. Rosiglitazone monotherapy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab 2001 86(l) 280-8. 

Raskin P, Rendell M, Riddle MC, Dole JF, Freed MI, Rosenstock JRosiglitazone Clinical Trials Study Group. A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Diabetes Care 2001 24(7) 1226-32. 

PTCA). The primary objective was to evaluate the occurrence of major adverse cardiac events (MACE) [death, recurrent myocardial infarction (Ml), or clinically driven target lesion revascularization] 30 days postprocedure. The secondary objectives were to evaluate the binary restenosis, incidence of (sub)acute stent thrombosis at 30 days follow-up, MACE at 6 and 12 months and the QCA endpoints at 6 months. This study was designed to allow a comparison with the patient population and the results of a larger randomized DISTINCT (BiodivYsio stent in controlled clinical trial) study previously conducted in the U.S. 

If the results of the clinical trial studies indicate that a new drug has potential therapeutic value that outweighs the risks associated with its proposed use, the manufacturer may seek authorization to sell the product in Canada by filing a New Drug Submission (NDS) with HPFB. 

Aldurazyme polymorphic variation of human a-L-iduronidase lysosomal hydrolase hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparin sulfate No genotoxicity studies clinical trials Studies to assess mutagenic and carcinogenic potential have not been conducted No warnings or precautions regarding carcinogenic risk... 

Phase I Clinical Trials Studies in this phase include initial introduction of an investigational drug into humans. These studies are closely monitored and are usually conducted in healthy volunteers. Phase I trials are conducted after the completion of extensive nonclinical or pre-clinical trials not involving humans. Phase I studies include the determination of clinical pharmacology, bioavailability, drug interactions and side effects associated with increasing doses of the drug. 

A particular problem in interpreting the beneficial role and efficacy of oximes in clinical practice is a deficiency of published data, especially those evaluated in controlled clinical trials. Studies related to the efficacy of oximes in a clinical setting showed the heterogeneity of therapeutic approaches (i.e. dose regimen, oxime choice, and final outcome of the treatment). 

Similarly, synthetic modification of castanospermine showed that the lipophilic 6-0-acyl derivatives were more potent inhibitors of HIV than the natural product. In particular, the 6-0-butanoyl derivative (MDL 28,574) was approximately twenty times more active than castanospermine and fifty times more active than A-butyl-DNJ. However, once inside cells, 6-0-butanoylcastanospermine appeared to be hydrolysed to release castanospermine and hence this compound can also be considered to be a pro-dmg. " Recently, this compound was reported to be tolerated well by patients during a phase II clinical trial. ° Studies in vitro have shown synergistic activity against HIV type 1 and 2 replication when castanospermine (and its 6-C>-butanoyI derivative) are combined with AZT and other similar dideoxynucleoside drags. ... 

Bronchoconstriction hr contrast to the minimal beneficial effects seen in cardiovascular disease clinical trials, studies of TP receptor antagonists, BAY U3405 and ICI 192605, have indicated beneficial effects on dmg-induced bronchoconstriction in humans (23,24). 

Phase I clinical trial studies include the initial administration of an investigational new drug to... 

Phase II clinical trial studies are designed primarily to explore the relationship between the dose level and frequency of administration and the efficacy and safety observed in patients with a particular therapeutic indication or disorder. Normally, a primary endpoint is selected to evaluate the efficacy however, secondary endpoints are often included to establish criteria for monitoring patients in the more definitive phase III clinical trials. Phase II clinical trials are commonly... 

Not all clinical trials, especially large, multisite, multinational phase III studies and phase IV postmarketing surveillance, pharmacoeconomic, and quality-of-life studies, can be conducted at a CSO facility. These types of studies, and many phase II efficacy studies, are conducted in research- or university-based hospitals or other investigational sites where a sufficient patient population with the disease or disorder to be tested is available. A number of CSOs offer services to support clinical trial studies that are implemented at one or more clinical trial sites. These services can be broken down into relatively broad categories, which are summarized later. 

Inflammatory Conditions. Many conditions associated with inflammation and increased oxidative stress could be influenced by selenium status. Positive effects from supplementation studies in arthritis and in pancreatitis have been reported. Low sermn selenium values are found in asthma, and some limited clinical trial studies show benefits firom supplementation." In a small trial in patients in intensive care with systemic inflammatory response syndrome (SIRS), high-dose selenium supplements over 9 days were associated with reduced incidence of renal failure and reduced mortality in the most severely fll. ... 

Define the following aspects of clinical trial study design ... 

Infliximab is approved for treatment of rheumatoid arthritis and Crohn s disease, but has been studied for use in psoriasis. One double-blind, randomized, placebo-controUed clinical trial studied the effectiveness and safety of infliximab in patients with moderate to severe psoriasis. A good response was seen in 82% and 91% of patients treated with infliximab 5 mg/kg or 10 mg/kg, respectively. Median time to response for all patients receiving infliximab was 4 weeks. The investigators concluded that patients treated with infliximab had a high degree of clinical improvement with rapid response rate, similar to that observed with cyclosporine therapy. ... 

Looareesuwan S, Chulay JD, Canfield CJ, Hutchinson DBA, for the Malarone clinical trials study group. Malarone (atovaquone and... 

Physicians who will conduct phase 1,2, and 3 clinical trial studies or serve as medical monitors if these studies are conducted by a CRO... 

Future Clinical Trials. Study C-04-59 is designed to evaluate the dose and administration frequency of anecortave acetate depot every three months (15 mg) or six months (15 or 30 mg). Inclusion criteria are similar to those of the previous trials. 

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