STUDY OF LONG-TERM ADMINISTRATION OF NATEGLINIDE AND VALSARTAN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is a multinational, randomized, double-blind, placebo-controlled, forced-titration 2 x 2 factorial design study of the efficacy and safety of long term administration of nateglinide and valsartan in the prevention of diabetws and cardiovascular outcomes in subjects with impared glucose tolerance (IGT). In addition, we will conduct a substudy to determine whether endothelial function and body composition predict the development of diabetes and cv events in patients with IGT. Patients from all 6 New Orleans Navigator study sites will be invited to participate in this sub study (which may also be incorporated as a substudy at other sites willing/able to carry out these procedures). Male and female subjects with impaired glucose tolerance on OGTT screening and greater than or equal to 1 cardiovascular risk factors (s) (RF) or greater than or equal to 1 cardiovascular disease (CVD) are eligible to participate. Approximately 1875 subjects will be randomized per treatment group. At the end of the core phase, the data will be analyzed for the time to progression to diabetes endpoint while the trial will continue in a blinded fashion. In case of a statistically significant effect of one or both drugs, submission of a registration dossier will be considered. If no statistical significance is reached by any of the drugs the trial will continue and the analysis of the cardiovascular morbidity/mortality endpoint will be exploratory. Approximately 7500 subjects from 600-800 centers in approximately 40 countries are to be randomized. Screening for eligibility will take place 1 month prior to treatment start and requires an oral glucose tolerance test (OGTT) to confirm eligibility. After receipt of the appropriate baseline data and cardiovascular disease status, eligible subjects will be randomly assigned to one of the four treatment groups (ratio 1:1:1:1), i.e. nateglinide 60 mg ac, valsartan 160 mg od, the combination of nateglinide 60 mg ac and valsartan 160 mg od, the combination of nateglinide 60 mg ac and valsartan l60 mg od, or placebo, using a computerized interactive voice response system (IVRS). Study accrual is expected to require approximately 18 months. The duration of study follow-up is fixed for the progression to diabetes endpoint at a minimum of 3 years from last-patient first-visit (LPFV). This duration also defines the duration of the core phase. For the cardiovascular endpoint, 1000 patients with an event are required. A total duration of follow-up of 5 years and 9 months after FPFV is anticipated.