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At least 109 records · Page 6Linked to original sources
PubMed1993

Clinical safety and tolerance of azithromycin in children.

An analysis of the safety data emanating from several clinical trials of the use of azithromycin in children has been undertaken. The studies compared azithromycin with standard regimens of various comparator agents: co-amoxiclav, amoxycillin, penicillin V, erythromycin, dicloxacillin and flucloxacillin, in the treatment of otitis media, pharyngitis and skin infections. Side-effects, based on the investigators' assessments of the severity and possible relationship to the study drugs, were measured within 35 days of the start of therapy. The total number of side-effects reported was significantly lower in the azithromycin-treated patients (46/606; 7.6%) than in the comparator-treated patients (72/523; 13.8%; P = 0.001). Two (0.3%) and five (1.0%) patients, respectively, withdrew from treatment in each group. The most frequently reported side-effects were gastrointestinal with an incidence of 5.6% (34 patients) in the azithromycin group and 11.7% (61 patients) in the comparator group (P < 0.001). The only other organ system with more than 0.5% of subjects reporting side-effects was the skin, with nine (1.5%) patients in the azithromycin and 11 (2.1%) patients in the comparator group complaining of dermatological reactions. Azithromycin was equally well tolerated in children of all ages. Inspection of individual studies showed no significant differences in laboratory test abnormalities between treatment groups. Overall, the most frequently (> or = 1% incidence) reported treatment-related laboratory test abnormalities were changes in neutrophil count (3.2%), lactate dehydrogenase (1.5%), blood urea (1.3%) and potassium (1.2%) in the azithromycin group; and in neutrophil (3.2%) and eosinophil count (2.1%) in the comparator group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Efaproxiral: a novel radiation sensitiser.

Efaproxiral (RSR13) is a synthetic allosteric modifier of haemoglobin that reduces its oxygen binding affinity. By facilitating the release of oxygen from haemoglobin, efaproxiral causes an increase in whole blood P 50 (partial pressure of oxygen which results in 50% haemoglobin saturation) and an increase in the PO2 (partial pressure of oxygen) in the tissue. The therapeutic strategy of enhancing oxygen unloading from haemoglobin to tissue emulates and amplifies physiological tissue oxygenation and can enhance the oxygenation of hypoxic tumours. Since hypoxia is known to decrease the effectiveness of radiation therapy, the use of efaproxiral as a radiation sensitiser may be advantageous. Unlike previous radiation sensitisers, efaproxiral does not need to enter the cancer cells to increase radiosensitivity. Phase I-III trial data have defined the safety profile and dosing of the drug, with the potential benefit for extended survival.

Aniline Compounds↗
PubMed2005

Meta-analyses and adaptive group sequential designs in the clinical development process.

The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control This enables a "seamless transition" from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.

Algorithms↗
PubMed2004

Therapeutic vaccine trails in Thailand.

An effective therapeutic HIV vaccine will not only benefit the HIV-infected person but will also provide invaluable information on effective immune response in designing or selecting a preventive vaccine. A phase II double-blind controlled clinical trial using HIV-1 immunogen (Remune) was undertaken in Thailand in 1995 in conjunction with phase III approval in the USA. In most instances, immune response to the virus was induced. The results from this study led to the extension of further trials over the following 4 years. At present, the Thai Food and Drug Administration (FDA) is in the process of reviewing the files on all information to assess the effectiveness of this therapeutic vaccine as well as reviewing the proposal to conduct a phase III trial to further confirm previous efficacy results from the phase II trials.

AIDS Vaccines↗
PubMedDate not supplied

A note on the power of Fisher's least significant difference procedure.

Fisher's least significant difference (LSD) procedure is a two-step testing procedure for pairwise comparisons of several treatment groups. In the first step of the procedure, a global test is performed for the null hypothesis that the expected means of all treatment groups under study are equal. If this global null hypothesis can be rejected at the pre-specified level of significance, then in the second step of the procedure, one is permitted in principle to perform all pairwise comparisons at the same level of significance (although in practice, not all of them may be of primary interest). Fisher's LSD procedure is known to preserve the experimentwise type I error rate at the nominal level of significance, if (and only if) the number of treatment groups is three. The procedure may therefore be applied to phase III clinical trials comparing two doses of an active treatment against placebo in the confirmatory sense (while in this case, no confirmatory comparison has to be performed between the two active treatment groups). The power properties of this approach are examined in the present paper. It is shown that the power of the first step global test--and therefore the power of the overall procedure--may be relevantly lower than the power of the pairwise comparison between the more-favourable active dose group and placebo. Achieving a certain overall power for this comparison with Fisher's LSD procedure--irrespective of the effect size at the less-favourable dose group--may require slightly larger treatment groups than sizing the study with respect to the simple Bonferroni alpha adjustment. Therefore if Fisher's LSD procedure is used to avoid an alpha adjustment for phase III clinical trials, the potential loss of power due to the first-step global test should be considered at the planning stage.

Analysis of Variance↗
PubMed2005

Technology evaluation: Chrysalin (Orthologic).

OrthoLogic (formerly Chrysalis) is developing Chrysalin, a synthetic 23-amino acid peptide that mimics a portion of human thrombin. The compound is in phase II clinical trials for the potential treatment of diabetic foot ulcers and phase III trials for cartilage repair and bone fractures.

Animals↗
PubMed2006

Drug evaluation: ranirestat--an aldose reductase inhibitor for the potential treatment of diabetic complications.

Ranirestat is an orally available aldose reductase inhibitor under development by Dainippon Sumitomo Pharma Co Ltd (formerly Dainippon Pharmaceutical Co Ltd), Kyorin Pharmaceutical Co Ltd and Eisai Co Ltd for the potential treatment of diabetic complications, such as neuropathy, cataracts, retinopathy and nephropathy. Phase III trials were ongoing in February 2006.

Aldehyde Reductase↗
PubMed2004

Bevacizumab for advanced colorectal cancer.

Bevacizumab is a recombinant humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF). It is thought that bevacizumab inhibits the formation of new blood vessels. Two clinical trials show that the addition of bevacizumab to a regimen of either fluorouracil plus leucovorin (FL) or FL combined with irinotecan (IFL), significantly improves response rate and time to tumour progression and increases overall survival for patients with advanced colorectal cancer (ACC). Thromboembolic events are the most clinically significant adverse events, but hypertension, hemorrhage and gastrointestinal perforation are other potential safety concerns. More studies are needed to compare the combination of bevacizumab plus IFL to other chemotherapy regimens used in the treatment of ACC. The addition of bevacizumab to 5-fluorouracil-based chemotherapy regimens will significantly increase the costs of palliation for ACC.

Antibodies, Monoclonal↗
PubMed1996

The role of bisphosphonates in the treatment of bone metastases--the U.S. experience.

Frequent complications of bone metastases include pain, pathologic fracture, hypercalcemia and spinal cord compression. Lytic bone metastases result from excessive activation of osteoclasts by tumor-produced cytokines. Aredia (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In two dose-seeking phase I trials in patients with breast cancer and prostate cancer, repeated intravenous infusion of Aredia was shown to be safe and effective in reducing bone resorption and pain. In a randomized phase III trial of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90 mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was associated with a significant decrease in bone pain and in the incidence and time to development of all skeleton-related events. Data from two phase III breast cancer trials each involving 300 patients are now being analyzed. The newer bisphosphonates can safely be used together with standard anticancer therapy to provide effective palliation of symptoms caused by lytic bone metastases.

Antineoplastic Agents↗
PubMed2005

Deferasirox Novartis.

Novartis is developing a chelating agent, deferasirox, as a once-daily oral therapy for the potential treatment of chronic iron overload in patients needing blood transfusions. By December 2004, data from a phase III trial for iron overload had been released, and filing is expected in the US and EU in the first half of 2005.

Administration, Oral↗
PubMedDate not supplied

An application of Bayesian population pharmacokinetic/pharmacodynamic models to dose recommendation.

Population pharmacokinetic data consists of dose histories, individual covariates and measured drug concentrations with associated sampling times. Population pharmacodynamic data consist of dose histories, covariates and some response measure. Population analyses, whether they be pharmacokinetic or pharmacodynamic attempt to explain the variability observed in the recorded measurements and are increasingly being seen as an important aid in drug development. In this paper a general Bayesian population pharmacokinetic/pharmacodynamic model is described and an analysis of data for the drug recombinant hirudin is presented. The model we use allows for both outliers and censoring in the concentration data and outlying individual pharmacokinetic parameters. We attempt to address directly important questions such as recommended dose size using predictive distributions for response.

Bayes Theorem↗
PubMed2005

Ranolazine CV Therapeutics.

CV Therapeutics, under license from Roche (formerly Syntex), is developing ranolazine (Ranexa), a metabolic modulator and a partial fatty acid oxidation inhibitor, for the potential treatment of angina and acute coronary syndromes. By October 2004, enrollment in the phase III MERLIN TIMI-36 study was ongoing and the company anticipated completion by the end of the first quarter of 2005.

Acetanilides↗
PubMed2002

[Chemotherapy of gastric cancer--a review of clinical trials in Japan].

This review focused on the clinical trials in patients with gastric cancer in Japan. Oral fluoropyrimidines have been extensively used in Japan. Through the decades, these oral fluoropyrimidines have been examined in a variety of combinations. Most of the reports are about randomized phase II trials using overall response rate as a primary endpoint, and are a few phase III trials were conducted. S-1 (TS-1), a novel oral fluoropyrimidine, has demonstrated promising activity in phase II trials. Ongoing phase III trials on S-1 would be defining this as standard chemotherapy for metastatic gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗