Phase II/III studies

At present, only acute cases of hepatitis E have been documented. There are no vaccines available to prevent hepatitis E however, a recombinant hepatitis E vaccine is undergoing Phase II/III study to determine its efficacy in preventing hepatitis E infections.49 Supportive care is the only treatment available for acute hepatitis E infection.19... 

In November 2005, a phase II/III study in NSCLC patients started in Australia and Canada, hi February 2006, Cediranib was undergoing a UK phase II/III trials in colorectal cancer. At that time, US phase II trials were underway in patients with advanced solid tumors, mesothelioma, melanoma, fiver, ovarian, peritoneal, fallopian tube, kidney, and breast cancers, hi May 2006, a US phase II trial began for neurofibromatosis type I and plexiform neurofibroma. 

Following the Umited success of this procedure, a multicenter phase II/III study is planned in European Union and the United States. The US component of the trial will study the effect of gene therapy in patients with stable angina. The EU component will evaluate patients with advanced coronary artery disease who are not considered candidates for interventions such as angioplasty or coronary artery bypass graft surgery. 

In a pooled analysis of 30 (26 controlled, 4 uncontrolled) prospective, phase II/III studies of oral or intravenous moxifloxacin in 8474 subjects no drug-related hypoglycemic events were reported (732). 

The described supportive study was specifically designed and suitably powered to identify differences in Drug XYZ pharmacokinetics between obese and non-obese. Typically this type of evaluation would be extended during the later clinical development by performing a population pharmacoki-netic/pharmacodynamic assessment of the impact of obesity on the disposition of the developmental drug during the phase II/III studies. 

This effect is more prominent in patients with low renin concentrations. The interaction of COX-2 inhibitors with ACE inhibitors has been much less well investigated. In a review of Phase II/III studies of COX-2 inhibitors, it was reported that the co-administration of rofecoxib 25 mg/day and benazepril 10-40 mg/day for 4 weeks was associated with an average increase in mean arterial pressure of about 3 mmHg compared with ACE inhibitor monotherapy (121). 

Krams, 2006) confidentiality and integrity issues (Gallo, 2006), dose-finding studies (Gaydos et cd., 2006), so-called seamless phase II/III studies (Maca et al, 2006) and sample size re-estimation (Chuang-Stein et al, 2006). 

Analysis of the database for age-related differences of efficacy, adverse events, dose, and (gender) relationships. A geriatric database may contain data from the main Phase II, III studies or from a geriatric-specific study. 

Usually, differences in the therapeutic response or adverse events are too small to detect at an equivalent plasma level between ordinary adult and elderly patients to make this a requirement. However, separate studies are requested of sedative hypnotic psychoactive drugs or drugs having a significant CNS effect, and, similarly, if Phase II, III studies are suggestive of an age-related difference. 

Paccagnella A, Oniga F, Bearz A, et al (2006) Adding gemcit-abine to paclitaxel/carboplatin combination increases survival in advanced non-small cell lung cancer results of a phase II-III study. J Clin Oncol 24 681-687... 

Where Phase II, III and IV studies are conducted in a hospital or contract research environment, it is strongly advisable to inform the subject s general practitioner (GP) in writing of the nature of the study and to obtain the GP s agreement, preferably in writing. This is essential for Phase 1 studies in non-patient volunteers, and it is routine practice in all Phase 1 clinical pharmacology units. However, increasingly, particularly in mainland Europe, study subjects will be found not to have a personal physician or, if they have, that their last visit to the physician could be a considerable time ago. 

Flutamide was the first drug used in prostate cancer therapy for which the withdrawal syndrome was reported. In that study, 40% of patients showed a decline in prostate specific antigen (PSA) levels after cessation of flutamide from the therapeutic protocol. The decline in PSA levels was associated with an improvement of the clinical symptoms. Based on these paradoxical observations, the concept of sequenced androgen ablation was proposed [217]. Several phase II clinical studies were performed, demonstrating safety and tolerability, however, a direct comparison in randomised phase III trials is necessary [218]. 

A phase II pilot study examined the effects of 120-h continuous infusion paclitaxel at two dose levels (105 mg/m2 and 120 mg/m2) when combined with conventional radiotherapy in 33 previously untreated patients with stage III/IV HNC (38). At the conclusion of treatment, 70% of patients had achieved a CR. The dose level of paclitaxel did not have an effect on the CR (p = 1). After 36 mo, locoregional control was achieved in 55.7%, OS of 57.8%, and DFS of 51.1% the median duration of survival was greater than 50 mo. 

In addition to the first in man studies there are subsequent studies in healthy volunteers, which are performed in parallel to the phase II/III clinical development. These studies address issues like drug-drug interactions, special sub-populations (e.g. patients with liver and renal impairment), or bioavailability/bioequivalence issues. These studies are also conducted under the same well controlled conditions and therefore contribute rich data. 

Not all clinical trials, especially large, multisite, multinational phase III studies and phase IV postmarketing surveillance, pharmacoeconomic, and quality-of-life studies, can be conducted at a CSO facility. These types of studies, and many phase II efficacy studies, are conducted in research- or university-based hospitals or other investigational sites where a sufficient patient population with the disease or disorder to be tested is available. A number of CSOs offer services to support clinical trial studies that are implemented at one or more clinical trial sites. These services can be broken down into relatively broad categories, which are summarized later. 

Assessment of vascularity can be useful in differentiating benign and malignant breast lesions using color Doppler examination. However, some neoplasms have low blood flow and Doppler may be suboptimal. In these cases, ultrasound contrast may be beneficial. In a phase II/III, multicenter, randomized study 220 patients... 

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