Clinical studies healthy volunteers

In a dose tolerance study, healthy volunteers were orally administered a combination of isolated bacosides A and B at doses of 20 to 200 mg daily for 4 weeks, or a single dose of 300 mg. No adverse effects were reported, and monitoring of clinical, hematological, and biochemical parameters did not reveal any drug-related abnormalities (Singh and Dhawan 1997). 

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. 

Eventually, the proposed method was successfully applied to quantify clarithromycin in spiked human plasma and real samples from healthy volunteers after oral administration of the dmg indicating the utility of this method for clinical and bioavailability studies. 

To date, three pharmaceutical companies have entered clinical trials with PHD inhibitors for the treatment of anemia with the most advanced being FG-2216. In clinical studies, compound 2 (likely FG-2216) showed a dose- and time-dependent elevation of plasma erythropoietin after oral administration [66]. Healthy volunteers were orally administered various doses of compound 2 and serum erythropoietin (EPO) concentrations were measured at various times. Compound 2 increased serum EPO levels in a dose-dependent manner and, following administration of the 20 mg/kg dose, a 5-fold increase of EPO levels was observed after 12 h. In the same patent application, the effect of 2 on anemic predialysis patients with no previous rh-EPO exposure was also disclosed. Patients were treated with 2 three times/week for 4 weeks (no dose reported) and the hemoglobin levels were assessed on day 42. The patients who received treatment showed a mean increase in hemoglobin of 1.9 g/dL from baseline values, whereas subjects who received placebo showed a mean decrease of 0.35 g/dL from baseline levels. These data suggest for the first time that an oral PHD inhibitor could be effective for the treatment of anemia. 

A study of GSK1278863A (structure undisclosed) in healthy adult subjects for the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat oral doses up to 300 mg for 14 days has also been completed [69]. Finally, AKB-6548 (structure undisclosed) has completed Phase la clinical trials in 48 healthy volunteers for the potential treatment of anemia. Preliminary results claim that doses that significantly increase plasma EPO without raising VEGF levels were identified and that further clinical trials are planned [70]. 

Clinical trials may be divided into three consecutive phases (Table 4.4). During phase I trials, the drug is normally administered to a small group of healthy volunteers. The aims of these studies are largely to establish ... 

Reminiscent of the trend with laboratory studies, most (33 out of 43 cited above) uncontrolled clinical trials with either healthy volunteers or cardiovascular patients suggest that oral and intravenous NO donors at therapeutic doses acutely inhibit platelet activation in vivo (vide supra). Aside from their lack of long-term dosing and a placebo control group, several considerations restrict the predictive clinical value of these uncontrolled clinical studies limited numbers of subjects nonuniform criteria for subject entry and treatment outside of the trial induction of adrenaline or... 

ICH E14 provides recommendations to sponsors concerning the design, conduct, analysis and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization. Specifically, it calls for a clinical thorough QT/QTc study (typically conducted in healthy volunteers), which is intended to determine whether a drug has a threshold pharmacological effect on cardiac repolarization, as detected by QT/QTc interval prolongation. 

Glund, K., Hoffmann, T., Demuth, H.-U., Banke-Bochita, J., Rost, K.-L. and Fuder, H. (2000) Single dose-escalation study to investigate the safety and tolerability of the DP IV inhibitor P32/98 in healthy volunteers. Experimental and Clinical Endocrinology and Diabetes, 108, 159. 

Phase I studies evaluate the pharmacokinetics and safety of the drug in a small number (tens) of healthy volunteers. Phase I studies are sometimes conducted in a small patient population (Proof of Concept studies) with a specific objective such as the validation of the relevance of preclinical models in man. The purpose of these studies may be the rapid elimination of potential failures from the pipeline, definition of biological markers for efficacy or toxicity, or demonstration of early evidence of efficacy. These studies have a potential go/no-go decision criteria such as safety, tolerability, bioavailability/PK, pharmacodynamics, and efficacy. Dosage forms used in Phase I or Proof of Concept studies must be developed with the objectives of the clinical study in mind. 

In this section, a brief summary of the nature, frequency, and consequences of adverse drug reactions (ADRs) in two clinical situations is presented. There are ADRs experienced by healthy volunteers and patients participating in clinical studies with potential new medicines and those experienced by patients who are prescribed licensed medicines. A review of these two situations points to areas of success with the current practices for non-clinical safety pharmacology testing but also identifies some areas where further research might lead to new or better safety pharmacology tests. Prior to reviewing the literature, some... 

The study was performed in patients exposed to ionizing radiation after Chernobyl accident. Comparison groups included patients and healthy individuals exposed to the natural radiation levels. Control group included healthy volunteers who resided in Kyiv since Chernobyl accident Distribution by diagnosis is presented at table 1. Investigated persons were at the age of 43-72 (mean+SD for the exposed group 52,3 + 10,1 yrs for control group- 46,3 + 11,3 yrs). All studied persons participated by informed consent. Peripheral blood and bone marrow samples were obtained by a standard procedure (National. Committee for Clinical Laboratory Standards, 1991). Flow... 

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