VITRO trial

A brief description of known mechanisms of resistance to the drug and results of any in vitro trials regarding resistance or any known epidemiological trials that demonstrate the prevalence of resistance factors. 

This section includes trials appropriate to a particular formulation or route of administration, such as in vitro hemolysis or irritation at the injection site. In vivo results should be tabulated to show group comparison and time-related or progressive effects within each group. For in vitro trials, the data should be tabulated by type of test or test system, dose range, and effects related to dose. 

In Vitro trials Conducted During the Clinical Trials... 

A 13-amino-acid polypeptide that mimicks the binding region of fertilin in step 2 inhibited fertilization in in vitro trials. 

In Vitro Trials. There were no significant effects on cellulose digestion where HC was added at levels of 1-15% to the standard assay system. 

As a result of the work cited and the in vitro trial herein reported, it was decided to prepare straw for in vivo trials by treating with 8 grams NaOH and 60 ml. of solution per 100 grams of straw. These levels although not resulting in the highest cellulose digestion in the in vitro experiment, minimized the quantity of alkali and water used with an... 

An in vitro trial of cranberry juice on human liver and rat small intestine microsomes demonstrated that cranberry juice significantly inhibited the activity of human and rat drug-metabolizing cytochrome P450 isoenzyme CYP3A... 

Attempts to establish the cause should as far as possible be carried out in vitro. Trial exposure to drugs on which the patient s history casts suspicion may lead to serious hemorrhages. If a provocation test is essential, the amount of drug administered should be very small, far below the normal dose. 

The preclinical trials are performed in in vitro and animal studies to assess the biological activity of the new compound. In phase 1 of the clinical trials the safety of a new drug is examined and the dosage is determined by administering the compound to about 20 to 100 healthy volunteers. The focus in phase II is directed onto the issues of safety, evaluation of efficacy, and investigation of side effects in 100 to 300 patient volimteers. More than 1000 patient volunteers are treated with the new drug in phase 111 to prove its efficacy and safety over long-term use. 

Dtugs in clinical development that directly target the A(3 pathway are at an early stage. Inhibitors of (3- and y-secretases that can lower the A 3 production have entered clinical phase trials with (3-secretase inhibitors being years behind the development of y-secretase inhibitors. Functional y-secretase inhibitors have been shown to reduce the rate of A 3 formation in vitro and in vivo. The reduction of A 3 monomer levels could prevent oligomer formation and subsequent syn-aptotoxicity. Numerous anti-amyloid approaches to... 

A large number of molecules have provided experimental evidence of neuroprotection in in vitro and in vivo models of Parkinson s disease and many of these putative neuroprotective substances are now the objects of clinical trials. Recently, a team of experts has identified potential neuroprotective agents to be tested in pilot studies [4]. Twelve compounds have been considered for clinical trials caffeine, coenzyme Q 10, creatine, estrogen, GPI1485, GM-1 ganglioside, minocycline, nicotine, pramipexole, ropinirol, rasagiline, and selegiline (for individual discussion see [4]). 

Vertex also put in clinical trial VX-765, another caspase-1 -specific, YVAD-derived peptidomimetic that is in vitro slightly more potent then pralnacasan (IC50 0.8 nM). Evaluation of VX-765 in a mouse model of oxazolone-induced dermatitis showed a dose-dependent (10-100 mg/kg) inhibition of ear inflammation. Consequently, VX-765 was enrolled in a 4-week phase Ila safety and pharmacokinetic study for psoriasis. However, Vertex has not communicated any results yet. 

Studies to investigate the safety and effectiveness of In Vitro Diagnostic (IVD) medical devices under intended use conditions are conducted as performance evaluations. They are considered to present less risk than clinical investigations since, by their nature, studies involving IVDs cannot have any direct impact on the health and safety of trial subjects. 

In-vitro diagnostic reagents for field trial studies should bear the statement For Investigational Use Only. The performance characteristics of this product have not been established. ... 

Saquinavir. SQV was first shown in vitro to have potent HIV-1 inhibition in acutely infected cells with an IC50 in the subnanomolar range and to inhibit viral maturation in chronically infected cells at 10 nM (Craig et al. 1991). Subsequently, clinical trials with SQV monotherapy in HIV-1 infected men at concentrations up to 600 mg three times a day for 16 weeks resulted in a decrease in HIV-1 RNA of 80% (0.71ogio) (Kitchen et al. 1995). These and other data facilitated SQV in becoming the first FDA-approved PI in December 1995. In its original formulation. 

Nelfinavir. Using structure-based design in conjunction with predicted oral pharmacokinetics, NFV was identified and found to have potent inhibition of HIV-1 in vitro with an IC50 in the 2nM range (Kaldor et al. 1997). Clinical trials of NFV revealed robust and sustained reductions in HIV-1 RNA with over half of all subjects attaining a persistent 1.6 logxo reduction at 12 months, in conjunction with a mean increase in CD4 cells of 180-200 per mm (Markowitz et al. 1998). In subjects... 

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