Volunteer observers

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. 

Subacute and chronic toxicity of alcohol and alcohol ether sulfates has been extensively tested in several animals and sometimes humans. The duration of the tests was in some cases as long as 2 years. When administered below the toxic amount no specific damages were observed in any of the species tested [333]. No severe side effects were observed in the study by Swisher, carried out with volunteers who ingested considerable amounts of anionic and nonionic surfactants over long periods [348]. Similarly, the effects produced by the intake of daily doses of 1 g of alcohol sulfate per person over 8 weeks [349],... 

When 100 mg of synthetic astaxanthin in olive-oil-containing meal was given to male volunteers, a maximum plasma concentration of 1.24 mg/L astaxanthin was observed in the first 6 hours postprandially. The relative concentration of total astaxanthin in HDL decreased compared to the other lipoprotein fractions in the 72-hour study. 

Based on a study conducted with 40 healthy volunteers, Lignell reported the effect of astaxanthin on mammalian muscle function. Volunteers received one capsule of 4 mg astaxanthin each morning in association with food. No significant difference was observed between the treatment and placebo groups in any physical parameters measured. 

Observations of the volunteers during the conduct of the field study... 

Observations of field activities are performed by one or more Field Scientists. Normally, each volunteer worker is observed by an individual Field Scientist. The Field Scientist must remain with the worker at all times and closely observe such activities as loading the chemical, spraying the field, harvesting, scouting, and cleanup activities. The Field Scientist should remain at a safe distance from the worker to avoid any serious exposure to the pesticide which may occur during the course of the replicate. Protective equipment may be necessary for the Field Scientist depending on expected exposure levels and the toxicity of the product. In any event, the Field Scientist should have anticipated the risk of close observation and be aware of what protective measures are necessary. 

There are situations where close-up observations of the volunteer study participant may not be warranted. For example, during a study to determine exposure to pesticides of a group of custom applicators using biological monitoring, observing the workers may not be acceptable in order to make sure that the exposure levels are not biased by any control of the study by the investigator. 

This study was conducted during all four seasons so any differences during hot and cold weather could be observed. All the participants were volunteers who wished to detoxify their systems as well as lose weight. 

In a subsequent study Bhambhani et al. (1997) observed significant increases in blood lactate concentrations in male and female volunteers exposed to 10 ppm hydrogen sulfide, although there was not a significant change in the activities of muscle lactate dehydrogenase, citrate synthase, or cytochrome oxidase. 

By administering both sizes of formulation simultaneously, a better discrimination of relative transit of the two phases can be made. In a cohort of 22 healthy young volunteers, an enteric-coated capsule was administered which contained tablets ("mTc-labeled 5 mm or 8.4 mm diameter) together with pellets (mIn-labeled 0.2 mm ion-exchange resin particles). The unit delivered the radiopharmaceuticals simultaneously to the ileocecal junction [44]. Under control conditions, no difference was observed between the rate of transit through the ascending colon of 0.2-mm particles versus 5-mm tablets, or 0.2-mm particles versus 8.4-mm tablets. The mean period of residence of 50% of the administered 0.2-mm particles in the ascending colon was 11.0 + 4.0 h. 

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. 

In humans, acute exposure to acrylonitrile results in characteristics of cyanide-type toxicity. Symptoms in humans associated with acrylonitrile poisoning include limb weakness, labored and irregular breathing, dizziness and impaired judgment, cyanosis, nausea, collapse, and convulsions (Baxter 1979). However, the doses that produce these effects were not clearly defined. Workers exposed to 16 to 100 ppm for 20 to 45 minutes complained of headaches and nausea, apprehension and nervous irritation (Wilson et al. 1948). The workers exposed to acrylonitrile vapors fully recovered. In a study with human volunteers exposed to acrylonitrile at doses of 2.3 and 4.6 ppm, no symptoms attributable to effects on the nervous system were observed (Jakubowski et al. 1987). 

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