Dosage trials

EXTENSIONS AND COMMENTARY Here is the chemical that is central to this entire book. This is the structural point of departure for every compound that is discussed here. It is the P in PIHKAL. It is without activity in man Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the Qualitative Comments given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, No effects, but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes. 

Tucker P, Zaninelli R, Yehuda R, et al. Paroxetine in the treatment of chronic posttraumatic stress disorder Results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 2001 62 860-868. 

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. 

Name and description of the investigational product(s). A summary of findings from non-clinical sfudies and from clinioal trials that is relevant to the trial. Summary of the known and potential risks and benefits, if any, to human subjects. Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s). A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Description of the population to be studied. References to literature and data that are relevant to the trial, and that provide background for the trial... 

Produce from trial animals may not enter the food chain unless authorised by the CVM on the basis of data showing that residues will be either safe or not present in produce from animals treated at the maximum dosage with the minimum allowed withdrawal period. The CVM must be notified of the date and place of slaughter at least 10 days prior to each shipment for slaughter. The regulations also address the retention of records and the competence of study investigators. Records of drug shipments must be maintained for at least 2 years after the date of shipment. Data and results of trials must be retained for either 2 years after completion of the trial, or... 

If food-producing species, a commitment that produce will not be used without prior authorisation, the approximate start and finish date of the trials, and information on the dosage and animals. 

Clinical situations in which detoxification is indicated can be grouped into three categories 1) for patients who have been taking a maintenance therapeutic dosage for moderate to long periods of time and for whom a trial without medication is warranted, 2) for patients taking supratherapeutic doses (usually in the context of benzodiazepine dependence), and 3) for patients who use benzodiazepines as part of mixed substance dependence. Detoxification should be approached differently in each category. 

SHELFLIFE.dat The content (% of nominal) of two active components in a dosage form was assayed at various times (0-60 months) during a pharmaceutical stability trial to determine the acceptable shelf-life of the formulation the point at which the lower 90% confidence limit of the finear regression model intersects the 90%-of-nominal line gives the answer. Use with SHELFLIFE or LINREG. 

The current use of IV rt-PA for acute stroke thrombolysis is based on the NINDS rt-PA study, a two-part randomized, double blind, placebo-controlled trial. " This trial was preceded by two open-label, dose-escalation safety studies that suggested that treatment within 180 minutes of stroke onset, and rt-PA dosages no higher than 0.95 mg/kg, was safe and effective. ... 

The Trial of Org 10172 in Acute Stroke Treatment (TOAST) was a randomized, double-blind, placebo-controlled trial of danaparoid in 1281 patients within 24 hours of onset of acute ischemic stroke. A three-stage dosage regime was used to achieve plasma anti-factor Xa activity of 0.8 unit/mL. Favorable outcome was defined as the combination of a Glasgow Outcome Scale (GOS) score of 1 or 2 and a modified Barthel Index (BI) score of 12 or greater (on a scale of 0-20) at 3 months or 7 days. Very favorable outcome required the combination of a GOS score of 1 and a Barthel Index (BI) score of 19 or 20 at 3 months or 7 days. 

In pharmaceutical and medical device development, clinical trials are classified into four main phases designated with Roman numerals 1,11, III and lY The various phases of development trials differ in purpose, length and number of subjects involved. Phase I trials are conducted to determine safe dose levels of a medication, treatment or product (National Institutes of Health, 2002). The main purpose is often to determine an acceptable single dosage - how much can be given without causing serious side-effects. Phase I trials will also involve studies of metabolism and bioavailabity (Pocock, 1983). The sample size of a Phase 1 clinical trial is usually small, ranging from 10-80 subjects (National Institutes of Health, 2002 Pocock, 1983). 

Reductions in HbAlc of 0.7%-0.8% were found in clinical trials verses placebo in both monotherapy and combination therapy using the recommended dose of sitagliptin 100 mg daily taken with or without food. Dosage adjustments to 50 mg and 25 mg daily are recommended for patients with moderate... 

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