Placebo-controlled studies phase

A number of studies have investigated the potential of melatonin to alleviate the symptoms of jet lag. Melatonin has been found to be effective in 11 placebo-controlled studies in reducing the subjective symptoms of jet lag such as sleepiness and impaired alertness (Arendt 2005). The most severe health effects of jet lag occur following eastbound flights, since this requires a phase advancement of the biological clock. In a recent study, phase advancement after melatonin administration (using 3 mg doses just before bedtime) occurred in all 11... 

Several placebo-controlled studies have demonstrated a significant delay in the need to initiate levodopa therapy in patients who receive selegiline in the early phase of the disease... 

The dataset used in this example comprised two phase III placebo-controlled studies used in the license application for oseltamivir (Tamiflu ). See Patel, Kay and Rowell (2006) for further details. Pre-defined symptoms consisted of cough, nasal congestion, headache, sore throat, fatigue, myalgia and feverishness and each of these was assessed on an ordinal scale none, mild, moderate, severe. Alleviation was recorded as the day on which all symptoms... 

Fluvoxamine. The second placebo-controlled study of a serotonin reuptake inhibitor in the treatment of social phobia to date involved fluvoxamine [Den Boer et al. 1994]. Thirty subjects with social phobia according to DSM-III-R criteria were randomly selected in a double-blind fashion in this 12-week study. At the end of this period, subjects who judged themselves as clinically improved were allowed to continue for an additional 12 weeks. Fourteen of 16 subjects in the fluvoxamine group opted to continue. No subjects in the placebo group proceeded into the follow-up phase of treatment. Fluvoxamine showed superiority to placebo on nearly all psychometric measures. 

Treatment of patients with high suicidal risk who are excluded from Phase I, O and m trials, especially from placebo-controlled studies. 

Hirsch FR, Dziadziuszko R, Thacher N, et al. Epidermal growth factor receptor immunohistochemistry comparison of antibodies and cutoff points to predict benefit from gefitinib in a phase 3 placebo-controlled study in advanced nonsmall-cell lung cancer. Cancer 2008 112 1114-21. 

Cardiotoxic effects are relatively uncommon with mianserin (2). In a placebo-controlled study in 50 patients with a variety of cardiac conditions who were taking anticoagulants, mianserin (up to 30 or 60 mg) had no effects on electrocardiography, blood pressure, or pulse rate after 3 weeks. In a second phase, mianserin (up to 60 mg/day) was compared with amitriptyline (up to 150 mg/day) and placebo in 18 healthy volunteers. Measurements included systolic time intervals, electrocardiography at rest and during exercise, echocardiography, and blood pressure. Amitriptyline had a negative inotropic effect mianserin increased ejection fraction. The results of both these experiments led the authors to conclude that mianserin is an antidepressant with very low cardiac toxicity. 

In a two-phase placebo-controlled study with an initial sample of 45 patients, 39 of whom completed the study, the addition of low doses of risperidone (0.5 mg/day) appeared to improve symptoms in patients with obsessive-compulsive disorder taking fluvoxamine monotherapy (51). The main adverse events included transient sedation and mildly increased appetite. 

Rao, S., Cunningham, D., de Gramont, A., Scheithauer, W., Smakal, M., Humblet, Y., Kourteva, G., Iveson, T., Andre, T., Dostalova, J., Hies, A., Belly, R., et al. (2004). Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. J Clin Oncol 22 3950-3957. 

In a phase-2, partly randomized, double-blind, placebo-controlled study of three different doses of abetimus in 58 patients, seven did not receive all doses because of adverse events (2). Five withdrew because of adverse events related to their lupus erythematosus non-renal exacerbations (n = 2), hematuria and hypertension (n — 1), worsening rash (n — 1), and nephritis (n — 1). One patient withdrew because of cellulitis and another because of a localized Herpes zoster infection. None of the reported adverse events was considered to be definitely related to the drug. 

Antin JH, Lee SJ, Neuberg D, Alyea E, Soiffer RJ, Sonis S, Ferrara JL. A phase Fll double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation. Bone Marrow Transplant 2002 29(5) 373-7. 

The efficacy and safety of tiagabine have been assessed in a study with an open screening phase (in which patients were titrated to the optimal tiagabine dose), followed by a double-blind, placebo-controlled, crossover phase (6). 

DITPA treatment improved left ventricular performance in rat and rabbit post-M I models of heart failure. In a double-blind, placebo controlled, pilot phase II clinical study in 19 patients with NYHA class II or III CHF in 2003, DITPA demonstrated a significant increase in cardiac index, as well as improvements in diastolic function, systemic vascular resistance, and cholesterol and triglyceride levels. In this study, DITPA was well tolerated, with no significant increase in heart rate or significant adverse events. Subsequently, a larger trial was initiated which, however, was discontinued in October 2006, based on a business decision by Titan. 

AG3340 (Prinomastat), a selective inhibitor of matrix metalloproteases, also inhibits retinal neovascularization in an animal model (63). Subsequently, a Phase II, randomized, double-masked, placebo-controlled study of the matrix metallopro-tease inhibitor AG3340 in patients with subfoveal CNV associated with AMD was conducted. The outcome of this study, however, was not released and the company decided not to proceed with a Phase III trial. 

---