Integration of modeling and simulation to support changes to ondansetron dosing following a randomized, double-blind, placebo-, and active-controlled thorough QT study.

Prolongation of the QT interval has been observed with ondansetron and other members of the 5-HT3 antagonist class. This is the first thorough QTc study of ondansetron conducted in accordance with ICH E14 guidelines, designed to investigate the effect of single intravenous (IV) doses of ondansetron on cardiac conduction compared to placebo and a positive control, moxifloxacin, in healthy subjects. Statistical analysis of dose-response showed the maximum mean difference in QTcF, compared to placebo and corrected for baseline (ddQTcF), was less than 10 milliseconds (ms) after an 8 mg IV dose and approximately 20 ms after the 32 mg dose, each infused over 15 minutes.

Effects of Esomeprazole on the Pharmacokinetics of Lapatinib in Breast Cancer Patients.

The aqueous solubility of lapatinib declines significantly at pH >4, suggesting that its bioavailability might be lowered by acid-reducing drugs. A study was therefore conducted to assess the effects of esomeprazole on lapatinib pharmacokinetics (PK). Women with metastatic human epidermal growth factor receptor 2 positive (HER2(+) ) breast cancer were enrolled.

Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory crossover study.

Context: Recently, a new oral prolonged-release formulation of morphine sulfate for once-daily dosing has been developed based on an injection-molded matrix (abuse-deterrent, prolonged-release erodible matrix [ADPREM]).

Objectives: The objective of this double-blind, randomized, exploratory crossover study was to assess the efficacy and safety of once-daily ADPREM compared with twice-daily controlled-release morphine (CRM; MST ContinusNapp Pharmaceuticals, Cambridge, UK).

Methods: Thirty-eight adult cancer pain patients participated in the study, which consisted of a run-in period for stabilization and two consecutive fixed-dose treatment periods of two weeks' duration each.

Relationship between depression severity entry criteria and antidepressant clinical trial outcomes.

Background: We assessed whether increasing the minimum prerandomization Hamilton Depression Rating Scale (HAM-D) score to enrich the severity of the depressed sample affects antidepressant trial outcome.

Methods: Using the Food and Drug Administration Summary Basis of Approval reports, we examined outcome data from 51 clinical trials (11,270 depressed patients) evaluating 10 investigational antidepressants.

Results: Using four categories of trials with increasing minimum HAM-D entry trial criteria, we found no statistically significant relationship between prerandomization categories and trial outcome overall.

Court-mediated disputes between physicians and families over the medical care of children.

Objective: To describe the judiciary's approach to parent-physician disputes over the care of sick children.

Data Sources: Court publications.

Study Selection: Fifty parent-physician disagreements over the care of children led to physician requests for court intervention and resulted in judicial opinions published by the court.

Analgesics for acute pain: Meeting the United States Food and Drug Administration's requirements for proof of efficacy.

Objective: To examine the United States Food and Drug Administration's (FDA) standards for reviews of the scientific basis for efficacy claims for newly approved oral analgesics.

Methods: Comparison of the trial methodologies and results provided by the FDA's medical reviewer in the Summary Bases of Approval (SBA) for the 9 oral acute analgesics approved in the last 10 years: ketorolac, diclofenac potassium, bromfenac, tramadol, hydrocodone/ibuprofen fixed combination, celecoxib, rofecoxib, tramadol/acetaminophen, and valdecoxib.

Results: For all 9 new analgesics, studies were conducted in patients with postoperative dental pain and nondental surgical pain.

The first 1000 dendritic cell vaccinees.

Dendritic cells (DCs) are potent antigen-presenting cells that have the ability to stimulate primary T cell antitumor immune responses in animals and humans. Since the first published clinical trial of dendritic cell vaccination in 1995, 98 studies describing more than 1000 vaccinees have been published in peer-reviewed medical journals or presented at the annual meetings of the American Society for Clinical Oncology, the American Association of Cancer Research, or the American Society of Hematology. Trials have been performed in 15 countries.