Clinical investigations, phases

The clinical development of new drugs usually takes place in steps or phases conventionally described as clinical pharmacology phase I), clinical investigation (phase II), clinical trials (phase III), and postmarketing studies (phase IV). Table 1.1 summarizes the four phases of clinical evaluation. 

In addition, inspections of clinical sites during the clinical investigation phase have risen and therefore the numbers of FDA-483s and warning letter for these issues have also increased. This means that compliance issues in relation to clinical trial activities could also delay the reviewer s final... 

Who Selected patients Why Therapeutic efficacy, dose range, kinetics, metabolism By whom Clinical pharmacologists and clinical Investigators PHASE 3... 

Einahy, all data, including the results of the clinical investigation, ate collected in a New Dmg Apphcation (NDA) and sent to the EDA. Once approved, the new dmg goes into production. After manufacturing begins, the new dmg products must be monitored in clinical use in the marketplace for reports of untoward reactions. This amounts to post-approval surveillance known as Phase IV. All such reports must be submitted to the EDA in a timely manner. 

Outline of any phase or phases of the planned clinical investigation... 

Where the drug studied is a racemate, the pharmacokinetics, including potential interconversion, of the individual enantiomers should be investigated in Phase I clinical studies. Phase I or II data in the target population should indicate whether an achiral assay, or monitoring of only one optical isomer where a fixed ratio is confirmed, will be adequate for pharmacokinetic evaluation. If the racemate has already been marketed and the sponsor wishes to develop the single enantiomer, additional studies should include determination of any conversion to the other isomer and whether there is any difference in pharmacokinetics between the single enantiomer administered alone or as part of the racemate. 

Very recently, preliminary clinical investigations have commenced with WEB 2086. In a double-blind and placebo-controlled phase 1 clinical trial, the drug completely inhibited PAF-induced ex vivo platelet aggregation 45 min after single oral administration of 20-400 mg [305], The effect of single... 

Approved clinical investigations follow three phases. In Phase 1, about 100 to 200 people are exposed to the drug to determine the tolerance, absorption, excretion, half-life, and other pharmacologic reactions the preferred route of administration and the safe dosage. In Phase 2, initial trials are conducted on 500 to 1000 patients to assess the treatment or prevention of the specific disease. Additional animal studies to indicate safety may be conducted concurrently. If these preliminary studies demonstrate sufficient promise. Phase 3 clinical trials are performed with several thousand patients. 

Selective COX-2 inhibitors are currently being investigated in cancer patients in phase I and early phase II clinical trials. The currently available data would suggest that specific inhibitors of COX-2 have the potential to increase the therapeutic ratio of radiotherapy in tumors that express COX-2, and that clinical investigation of this interaction is warranted. 

Adequate information to assure proper identification, quality, purity, and strength of the investigational drug. The amount of information required depends on the phase of the study, the study duration, the dosage form, and the scope of the proposed clinical investigation. Information should be updated throughout the development process and scale-up of drug production. 

Clinical protocols and investigator information—detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. Also, information on the qualifications of clinical investigators—professionals (generally physicians) who oversee the administration of the experimental compound—to assess whether they are qualified to fulfill their clinical trial duties finally, commitments to obtain informed consent from the research subjects, to obtain review of the study by an IRB, and to adhere to the IND regulations. 

Clinical investigations are clearly the most critical and demanding stage in the new dmg development phase. When a dmg company believes it has sufficient preclinical testing data to show that a new dmg candidate is adequately safe for initial small-scale clinical studies, the company assembles and submits an investigational new dmg (IND) application in the United States or a clinical trial application (CTA) in the European Union. The IND or CTA is the prerequisite for a company to obtain... 

The formulation, manufacturing process, analytical development, and long-term toxicology studies in animals are parallel to the clinical investigation (Table 1.1). Clinical trial materials should be developed, manufactured, tested, and released before conducting a phase I clinical trial. Process chemists may redesign the synthetic route for the dmg candidate to meet the requirements of large-scale production in a pilot plant. Preformulation scientists complete the activities of salt selection,... 

---