Safety trial

Sanchez-Ramos J., Mash D. Ibogaine Human Phase I Pharmacokinetic and Safety Trial. FDA IND. 3968, 1993 (revised 1995). 

Phase I Initial safety trials on a new medicine in which investigators attempt to establish the dose range tolerance for single and multiple doses in about 20-80 healthy volunteers. 

Phase I. Initial safety trials on a new medicine, usually conducted in normal male volunteers. An attempt is made to establish the dose range tolerated by volunteers for single and for multiple doses. Phase I trials are sometimes conducted in severely ill patients (e.g., in the field of cancer) or in less ill patients when pharmacokinetic issues are addressed (e.g., metabolism of a new antiepileptic medicine in stable epileptic patients whose microsomal liver enzymes have been induced by other antiepileptic medicines). Pharmacokinetic trials are usually considered Phase I trials regardless of when they are conducted during a medicine s development. 

FDA Perspective on Genotyping and Clinical Efficacy/Safety Trials 220... 

Savitsky JP, Doczi J, Black J, et al. A clinical safety trial of stroma-free hemoglobin. Clin Pharmacol Ther 1978 23 73. 

The first information to come to light will be on the pharmacokinetics of newly approved drugs in children and adolescents simply because such studies are faster to complete than are clinical trials for efficacy, safety, and tolerability. Such pharmacokinetic data can aid the determination of the optimal dose and dosing schedule for the efficacy/safety trials (34, 35 and 36). 

In October 2004, clinical data from a phase I safety trial of OTI-OIO therapy for the treatment of GVHD were reported. Infusion of hMSCs decreased GVHD in 22 to 45% of patients, suggesting that OTI-OIO reduces the numbers of pro-inflammatoiy cytokines and T-cells while increasing levels of anti-inflammatory cytokines in these patients [570810]. 

For these reasons, determining the nature, predictability, and reversibility of immune system effects become a critical factor in weighing the risk-benefit ration of an phase 1 trial in healthy volunteers, as well as the determining a safe starting dose, safe maximum dose, and methods for monitoring potential immunotoxicity in these subjects. Over the past decade single-dose PK and safety trials of biopharmaceuticals in healthy volunteers have often preceded initial patient studies, even for products with known immunomodulatory effects at the anticipated therapeutic chronic dose exposure. 

Einally, pharmacokinetics in the efficacy/safety trial population are essentially similar to pharmacokinetics in healthy subjects, and no patient-specific factor warranting clinical consideration of dose regimen adjustment was identified in these analyses [65]. 

What dose escalation scheme should be used for the early clinical safety trials ... 

In all, 193 experiences nucleaires (nuclear tests and safety trials) were conducted at the French nuclear weapon test site at Mururoa and Fangataufa atolls. Of these, 178 were nuclear tests , in which a nuclear device was exploded with a large release of fission and, in some cases, fusion energy and 15 were safety trials in which more or less fully developed nuclear devices were subjected to simulated accident conditions and the nuclear weapon cores were destroyed by means of conventional explosives, with no or—on a few occasions—very small releases of fission energy. 

French atmospheric nuclear tests and safety trials at Mururoa and Fangataufa Atolls ... 

Safety trials were conducted to investigate the behaviour of the core of a nuclear device under simulated faulty detonation conditions. The core is destroyed by the conventional explosive detonation of such a device, with the production of finely divided plutonium and plutonium oxide which are widely dispersed if the test is not confined. Usually no fission takes place, though there was a very small fission energy release in three of the French underground safety trials. (Since there was some explosive yield, these three trials are sometimes counted as nuclear tests which would put the total number of underground nuclear tests at Mururoa and Fangataufa atolls at 140 rather than 137.) All of the 15 safety trials were carried out at Mururoa. 

Of the 15 safety trials, five were carried out in the atmosphere and ten underground. The five atmospheric safety trials were conducted between 1966 and 1974 on the surface at the northern tip of the atoll on the three motus of Colette, Ariel and Vesta. The ten underground safety trials were performed in the north-eastern part of Mururoa Atoll, three in vertical drilled shafts that penetrated from the rim into the volcanic rock. 

It was three of the safety trials that took place in the carbonate rock that had small releases of fission energy associated with them. 

Each safety trial reportedly involved 10 TBq of If the material used in these... 

The safety trials The safety trials conducted at the northern tip of Mururoa Atoll on the motus of Colette, Ariel and Vesta have left some particulate plutonium on the surface in that area, despite extensive cleanup operations carried out in 1982-1987 and in an adjacent sand bank in the lagoon. 

Several kilograms of plutonium resulting from the atmospheric nuclear tests carried out at the atolls remain in sediments under the lagoon of each atoll. Some of the plutonium in the sediments of the Mururoa Atoll lagoon came from the atmospheric safety trials. 

Particles containing plutonium and small amounts of americium resulting from atmospheric safety trials remain in the area of the trial sites—the motus of Colette, Ariel and Vesta on Mururoa Atoll. The Study analysed these types of particles, found in samples of sand and coral collected from the surface of the motu of Colette and in sand taken from a sandbank adjacent to it. 

Cohen A, Galanello R, Piga A, Vullo C, Tricta F. A multicenter safety trial of the oral iron chelator deferiprone. Ann NY Acad Sci 1998 850 223-6. 

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