Clinical studies/trials control

Clinical trials must be conducted to establish safety in each target animal species which, in the majority of cases, will include food-producing species. Although the same types of animal may be involved in both pre-clinical and clinical trials, dear distinctions can be drawn between each type of study. Pre-clinical studies are only conducted in animals that are kept for the purposes of laboratory research, and that are usually maintained in a very controlled environment. Clinical trials, on the other hand, are conducted in animals that are representative of the normal conditions (field conditions) and purposes for which they are maintained. 

Kranzler HR, Bauer LO, Hersh D, et al Carbamazepine treatment of cocaine dependence a placebo-controlled trial. Drug Alcohol Depend 38 203-211, 1995 Levin FR, Lehman AF Meta-analysis of desipramine an adjunct in the treatment of cocaine addiction. J Clin Pharmacol 11 374-378, 1991 Lima MS, Reisser AA, Soares BG, et al Antidepressants for cocaine dependence. Cochrane Database Syst Rev 4 CD002950, 2001 Ling W, Shoptaw S, Majewska D Baclofen as a cocaine anti-craving medication a preliminary clinical study 0etter). Neuropsychopharmacology 18 403 04, 1998... 

Grover NB. Reporting laboratory results to clinical centers through the study website. Controlled Clin Trials 2004 P39. 

An overall osteoprotective effect is associated with soy diets, the major active component being the isoflavones although the contribution (if any) of soy protein has to be clarified. The spine, rather than the femur, appears to be the most consistently protected bone site. The average daily intake in Japanese women is around 50 mg/day and appears to be sufficient to have a long-term protective effect on the spine. In non-Asian, postmenopausal women, the demonstrated effective dose is 80-90 mg/day. In future clinical studies, investigating the effect of isoflavones on bone metabolism, larger scale, randomized, controlled, intervention trials for longer time periods (1-3 years) will be necessary with a standardized source of soy protein/isoflavones and... 

Rimonabant (382) was also included in a clinical study to assess the safety and efficacy of four novel compounds for the treatment of schizophrenia and psychoaffective disorder [378]. The other compounds included in the trial were a neurokinin NK3 antagonist, a serotonin 2A/2C antagonist and a neurotensin NTSl antagonist. Halopeiidol and placebo groups were used as controls in the study. Sixty-nine patients received (382) (20 mg once per day), which failed to demonstrate efficacy in this trial. The reasons for the lack of efficacy may be due to inadequate dosing or an indication that CBi antagonism is not appropriate in the treatment of this condition. 

Interest in the role of HMG-CoA reductase inhibitors (statins) in the treatment of osteoporosis came from boneforming properties seen in animal studies. However, controlled clinical trials are needed. 

One aspect of the labeling deserves special mention. The Clinical Efficacy Trials subsection within the Clinical Pharmacology section not only describes the clinical trials providing evidence of citalopram s antidepressant effects, but makes mention of adequate and well controlled clinical studies that fail to do so. I... 

When we began using reserpine at the Maudsley Hospital less than two years ago there were very few reliable accounts of its use in the treatment of neuropsychiatric conditions and almost no controlled clinical studies. Dr D. L. Davies and I therefore conducted a clinical trial on a mixed group of out-patients, the majority of whom were suffering from anxiety and depressive reactions. The patients were given either reserpine, prescribed as Serpasil in a dose of 0.5 mg. by mouth twice daily, or a seemingly identical placebo, for a period of six weeks. The two substances... 

Pre-approval safety and efficacy clinical studies involved product administration to 2500 adults with either type-1 or -2 diabetes. The primary efficacy parameter measured was glycaemic control (as measured by the reduction from baseline in haemoglobin Ale). Hypoglycaemia was the most commonly reported adverse effect. Trials also showed a greater decline in pulmonary function in the Exubera group, and product should not be administered to patients with underlying lung disease, or to smokers. Exubera was developed by Nektar Inc. and is marketed under licence by Pfizer. 

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... 

Phase IV. Studies or trials conducted after a medicine is marketed to provide additional details about the medicine s efficacy or safety profile. Different formulations, dosages, durations of treatment, medicine interactions, and other medicine comparisons may be evaluated. New age groups, races, and other types of patients can be studied. Detection and definition of previously unknown or inadequately quantified adverse reactions and related risk factors are an important aspect of many Phase IV studies. If a marketed medicine is to be evaluated for another (i.e., new) indication, then those clinical trials are considered Phase II clinical trials. The term postmarketing surveillance is frequently used to describe those clinical studies in Phase IV (i.e., the period following marketing) that are primarily observational or nonexperimental in nature, to distinguish them from well-controlled Phase IV clinical trials or marketing studies. 

Melatonin does appear to initiate sleep effectively, but its extremely short duration of action raises questions about its ability to sustain sleep through the night. The effective dose of melatonin is not known. It has not yet been well studied in controlled clinical trials, and inaccuracies in the reported dosage of many dietary supplements remain a problem. 

The Medicines Act 1968 included the definitions of a clinical trial and of a medicinal product. Clinical studies involving healthy volrmteers did not meet this definition of a clinical trial and, as a result, did not come under the remit of regulatory controls. Such studies were subject to self-regulation by the pharmaceutical industry. Consequently, only the clinical trials in patients had to be covered by a clinical trial certificate (CTO. 

During placebo-controlled clinical trials in the US, a total of 0.26% pioglitazone-treated patients and 0.25% placebo-treated patients had ALT values 3 times or more the ULN. During all clinical studies in the US, 0.43% pioglitazone-treated patients had ALT values 3 times or more the ULN. 

The first 24-hour dose may be individualized for each patient however, in controlled clinical trials, mean daily doses greater than 2100 mg were associated with an increased risk of hypotension. The initial infusion rate should not exceed 30 mg/min. Based on the experience from clinical studies, a maintenance infusion of up to 0.5 mg/min can be cautiously continued for 2 to 3 weeks regardless of the patient s age, renal function, or left ventricular function. There has been limited experience in patients receiving amiodarone IV for more than 3 weeks. 

Biliary excretion As most entacapone excretion is via the bile, exercise caution when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone (see Drug Interactions). Lab test abnormalities Entacapone is an iron chelator. The impact of entacapone on the body s iron stores is unknown however, a tendency towards decreasing serum iron concentrations was noted in clinical trials. In a controlled clinical study, serum ferritin levels (as a marker of iron deficiency and subclinical anemia) were not P.764... 

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