Disease relevance of Clinical Trials, Phase III

• The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies [1].
• Because progesterone antagonists are growth inhibitors, they are in Phase III clinical trials for the treatment of breast cancer [2].
• Tirapazamine (TPZ), a bioreductive drug with selective toxicity for hypoxic cells in tumors, is currently in Phase III clinical trials [3].
• The change of brain lesion load, measured on T2-weighted magnetic resonance imaging (MRI) using computer-assisted techniques, is a widely used secondary endpoint for phase III clinical trials in multiple sclerosis (MS) [4].
• METHODS: Combined results are reported from 2 phase III clinical trials in which a total of 497 subjects with primary Sjögren's syndrome received 150 international units of human IFN alfa or matching placebo 3 times per day for 24 weeks by the oromucosal route [5].

High impact information on Clinical Trials, Phase III

• Phase 3 clinical trials investigating first- and second-generation P-gp antagonists have yielded conflicting results, emphasizing the importance of applying preclinical principals to realistically appraise expectations for clinical benefit [6].
• The NtRTI furthest along the developmental process is tenofovir disoproxil fumarate (TDF), an orally available acyclic adenine phosphonate analogue, currently in Phase III clinical trials [7].
• Two of them, Macugen and E2F decoy, are in phase III clinical trials [8].
• CONCLUSION: The activity of topotecan in extensive-stage SCLC noted in this study warrants further investigation of this agent in phase III clinical trials [9].
• Misonidazole (MIS) is a hypoxic cell radiosensitizer currently undergoing Phase III clinical trials in the treatment of cancer by radiation [10].

Chemical compound and disease context of Clinical Trials, Phase III

• The safety of flurbiprofen (Ansaid, Upjohn) was assessed after pooling data on kidney and liver function collected from nine separate phase III clinical trials involving 1,677 patients (941 receiving flurbiprofen and 736 receiving comparison drugs) with ankylosing spondylitis, osteoarthritis, or rheumatoid arthritis [11].
• Adefovir dipivoxil [bis(pivaloyloxymethyl)-ester prodrug], an orally bioavailable prodrug of adefovir [9-(2-phosphonylmethoxyethyl)adenine], is currently in phase III clinical trials for the treatment of human immunodeficiency virus (HIV) [12].
• 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methyluracil (L-FMAU; Clevudine) is a thymidine analog that is currently under phase III clinical trials as an anti-human hepatitis B virus agent [13].
• 1 Losigamone is a novel anticonvulsant undergoing phase III clinical trials in patients with partial and secondary generalized seizures [14].
• As yet, only UFT/leucovorin and capecitabine have been evaluated in randomized phase III clinical trials in metastatic colorectal cancer [15].

Biological context of Clinical Trials, Phase III

• Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials [16].
• CONCLUSIONS: The results from the 3 pharmacokinetic studies reviewed demonstrate the bioequivalence of the ER and IR formulations and support the use of this clarithromycin ER formulation in a once-daily dosing regimen in phase III clinical trials [17].
• Sanazole (AK-2123) (N-2'-methoxy ethyl)-2-(3"-nitro-1"-triazolyl)acetamide, which has completed phase III clinical trials as a radiosensitizer, enhanced gamma-radiation induced apoptosis in murine fibrosarcoma upon i.p. administration at 40 mg/kg body weight one hour prior to irradiation [18].
• The novel immunomodulator FTY720 is effective in experimental models of transplantation and autoimmunity, and is currently undergoing Phase III clinical trials for prevention of kidney graft rejection [19].
• Tesaglitazar is a dual-acting PPARalpha/gamma agonist currently being investigated in phase III clinical trials as an alternative treatment for insulin resistance and the characteristic dyslypidemia of type 2 diabetes [20].

Anatomical context of Clinical Trials, Phase III

• Onconase is a 12 kDa protein homologous to pancreatic RNase A isolated from amphibian oocytes which shows cytostatic and cytotoxic activity in vitro, inhibits growth of tumors in mice and is in phase III clinical trials [21].
• The results from two randomized double-blind phase III clinical trials in patients with breast cancer treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim [22].
• Currently, tirilazad is being actively investigated in phase III clinical trials in head and spinal cord injury, ischemic stroke and subarachnoid hemorrhage [23].

Associations of Clinical Trials, Phase III with chemical compounds

• cis-trans-cis-Ammine(cyclohexylamine)diacetatodichloroplatinum(IV) is an oral analog of the platinum anti-cancer drug cisplatin that is currently in phase III clinical trials [24].
• Cilomilast (Ariflo, SB 207499, SmithKline Beecham), the most advanced member of the class in Phase III clinical trials, was reported to have a limited therapeutic window [25].
• Indinavir did not increase the short-term risk of adverse cardiovascular events relative to nucleoside reverse transcriptase inhibitor therapy in four phase III clinical trials [26].
• These data does not support the need for phase III clinical trials to test efficacy of vitamin E in SSc [27].
• PURPOSE: G3139 is an antisense bcl-2 phosphorothioate oligodeoxyribonucleotide that is currently being evaluated in Phase III clinical trials in several human cancers [28].

Gene context of Clinical Trials, Phase III

• Moreover, BS-RNase monomers described herein are more toxic to human tumor cells than is any known variant or homologue of RNase A including Onconase, an amphibian homologue in phase III clinical trials for the treatment of unresectable malignant mesothelioma [29].
• The most promising COX/5-LOX inhibitor is ML3000 ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid), now in Phase III clinical trials [30].
• PTK/ZK is a novel, oral angiogenesis inhibitor that specifically targets all 3 vascular endothelial growth factor (VEGF) receptor tyrosine kinases and is currently in phase III clinical trials [31].
• We include data from three phase III clinical trials, comparing the activity of the new-generation aromatase inhibitors, anastrozole or letrozole, with tamoxifen as a first-line treatment [32].
• As specific NHE1 inhibitors have finished Phase II/Phase III clinical trials for myocardial protection, there is the possibility for a rapid biological translation of this novel therapeutic strategy to a clinical setting [33].

Analytical, diagnostic and therapeutic context of Clinical Trials, Phase III

• Using the computer program COMPARE to search the database established by the Anticancer Drug Screening Program of the National Cancer Institute, a possible mechanism-based correlation was found between onconase, an antitumor ribonuclease currently being evaluated in phase III clinical trials, and the chemotherapeutic agent bleomycin [34].
• Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a myocardial perfusion imaging agent demonstrating significant redistribution and currently in phase III clinical trials [35].
• BACKGROUND: Daclizumab (Zenapax, Roche Pharmaceuticals), a humanized monoclonal antibody directed against the alpha chain of the interleukin 2 receptor, has been shown to reduce the incidence of acute rejection at 6 months after renal transplantation in two phase III clinical trials [36].
• The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials [37].
• The results of three randomized phase III clinical trials of single-agent docetaxel (Taxotere, Rhône-Poulenc Rorer, Collegeville, PA) 100 mg/m2 every 3 weeks in comparison to combination chemotherapy regimens in patients with metastatic breast cancer pretreated with an anthracycline-based chemotherapy regimen are reviewed and reported [38].

References