Phase elderly patients

Aniracetam (6), launched in 1993 in both Japan and Italy for the treatment of cognition disorders, is in Phase II trials in the United States as of this writing. In clinical studies it has been shown to cause some improvement in elderly patients with mild to moderate mental deterioration (63), and in geriatric patients with cerebral insufficiency (64). In a multicenter double-blind placebo-controUed trial involving 109 patients with probable AD, positive effects were observed in 36% of patients after six months of treatment (65), a result repeated in a separate study of 115 patients (66). A review of the biological and pharmacokinetic properties, and clinical results of aniracetam treatment in cognitively impaired individuals is available (49). 

A phase II study of EVT-201, a partial positive modulator of GABAa receptor, has recently been initiated in the US in elderly patients with chronic insomnia with the maintenance as primary endpoint (no structure disclosed). 

The cost of drug development continues to spiral upward. Inflation and increased regulatory requirements, however, only account for a small portion of this increase. At this time, productivity is a major issue. A review of 198 new drug candidates that reached phase I clinical studies indicates a 60% failure rate due to poor pharmacokinetic properties or toxicity [23]. On the average, less than 2% of the drug failures could be attributed to drug interactions that resulted in adverse reactions [24], In elderly patients, however, drug interactions could contribute... 

VPA may also benefit the maintenance and the prophylactic phases as well, but there are only limited data in this regard, in contrast to lithium, which remains the best-studied maintenance therapy. VPA has a favorable and relatively safe side effect profile compared with other agents and can be combined with other commonly used psychotropics without significantly altering their metabolism or compromising adequacy of blood levels ( 155). There are also limited anecdotal data that this agent can be safe and effective in the elderly patient (156, 157). 

Whereas iithium has been the standard approach, increased complications in elderly patients, especially when there is compromise of the CNS, endocrine, or renal systems, makes this agent a less attractive choice. Lower doses (e.g., 150 to 300 mg) should be initiated, with many elderly patients achieving adequate response on total daily doses of lithium in the 450- to 600-mg range. If a more rapid response is necessary, low-dose high-potency antipsychotics can also be used in the early phases. Alternatively, a BZD, such as clonazepam or lorazepam, may be indicated (297). 

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 and III studies are suggestive of an age-related difference. 

Lowenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65 + years with acute myeloid leukemia a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol 1989 7 1268-1274. 

Press release, (17 April 2007) GTx announces Ostarine improved insulin resistance among elderly patients in a recently completed phase II clinical trial, http //www.gtxinc.com. 

In other cases, a new dosage formulation is required to satisfy a new market segment. Oral solutions and chewable tablets are beneficial for a pediatric population. A slow-release preparation (such as percutaneous patches) may be preferred in elderly patients taking multiple drugs if it allows once-daily (or less frequent) dosing. Trials demonstrating safety and efficacy of new formulations are often conducted in Phase IV and typically act as the supporting information for an sNDA. 

In an analysis of phase HI studies, changes in vital signs did not differ between patients given linezolid and comparator drugs (i.e. antibiotics) when either were used with drugs known to interact with MAOIs, including unnamed cyclic antidepressants. A case report describes the serotonin syndrome in an elderly patient treated with linezolid 600 mg every 12 hours, 21 days after amitriptyline 10 mg daily, paroxetine 20 mg daily and alprazolam 500 micrograms daily were started. ... 

Wijermans P, Liibbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A. Low-dose 5-aza-2 -deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome a multicenter phase II study in elderly patients. J Clin Oncol 2000 18(5) 956-62. 

Kudoh, S., Takeda, K., Nakagawa, K., et al. (2006). Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J. Clin. Oncol. 24, 3657-3663. 

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