Schematic Representation of Study Design. Approximately 1250 subjects will be randomized *** at up to *** study sites. The randomization schedule will be stratified by *** to ***; at least *** of subjects enrolled into the study will be ***. Subjects will initiate treatment with a dose titration during weeks 1-4 with doses gradually increased at *** intervals, as determined by randomization assignment, until the specified dose is reached and will be treated for 52 weeks (weeks 5-56) at the assigned dose level. Subjects will return to the site at the end of weeks 2 and 4 (Visits 3 and 4) during titration and at 4-week intervals thereafter. A schedule of events is provided in Appendix 1. The primary endpoints are differences between *** and *** groups in mean percent loss of baseline body weight, determined by weight at randomization (baseline) and weight at end of treatment (week 56), and percent of subjects with weight loss of 5% or more at end of treatment (week 56). Percent weight loss will be calculated as ***. Secondary efficacy endpoints are: · The difference in absolute weight loss between randomization (baseline) and end of treatment (week 56) for *** and *** groups. · The difference in percent of subjects who achieve a reduction in total body weight of at least 10% between randomization (baseline) and end of treatment (week 56) for *** and *** groups. · The difference in change in waist circumference (randomization to week 56) for *** and *** groups. Additional efficacy endpoints will include the effect of treatment on obesity-associated cardiovascular risk factors (total cholesterol, triglycerides, LDL-C, HDL-C, fasting glucose, blood pressure), ***, *** of *** and *** and ***, *** and ***. The difference between *** and *** groups in the rate of progression to type 2 diabetes will be calculated. Baseline adjusted Framingham 10-year risk scores will be calculated and compared between groups at weeks 28 and 56. Change in BMI between baseline and week 28 and end of treatment (Visit 17, week 56) will be evaluated. Additionally, body composition will be assessed by *** at ***. These evaluations will be made at ***, and at *** and ***. The change in weight loss (percent, absolute, percent of subjects achieving weight loss of > 5% and > 10% of starting weight), waist circumference and obesity associated risk factors will also be assessed over time. Subgroup analyses, including but not limited to analysis by gender, age and race, may be performed. Safety evaluations will include assessment of adverse events, including eye symptoms, ***. *** will also be obtained, and effects of various cofactors including (but not limited to) ***, gender, race, ***, and age will be evaluated. ***.
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Schematic Representation of Study Design. Approximately 1250 2500 subjects will be randomized *** at up to *** study sitessites in the United States. The randomization schedule will be stratified by *** to ***; at least *** of subjects enrolled into the study will be ***. Subjects will initiate treatment with a dose titration during weeks 1-4 with doses gradually increased at *** intervals, as determined by randomization assignment, until the specified dose is reached and will be treated for 52 weeks (weeks 5-56) at the assigned dose level. Subjects will return to the site at the end of weeks 2 and 4 (Visits 3 and 4) during titration and at 4-week intervals thereafter. A schedule of events is provided in Appendix 1. The primary endpoints are differences between *** and *** groups in mean percent loss of baseline body weight, determined by weight at randomization (baseline) and weight at end of treatment (week 56), and percent of subjects with weight loss of 5% or more at end of treatment (week 56). Percent weight loss will be calculated as ***. Secondary efficacy endpoints are: · The difference in absolute weight loss between randomization (baseline) and end of treatment (week 56) for *** and *** groups. · The difference in percent of subjects who achieve a reduction in total body weight of at least 10% between randomization (baseline) and end of treatment (week 56) for *** and *** groups. · The difference in change in waist circumference (randomization to week 56) for *** and *** groups. Additional efficacy endpoints will include the effect following: · Effect on ***; · Effect on *** of treatment on *** and ***; ***, *** and ***; · Change from baseline to week 28 and week 56 in BMI; · The change in obesity-associated cardiovascular risk factors markers (total cholesterol, triglycerides, LDL-C, HDL-C, HgbA1c, fasting glucose, fasting insulin, a measure of insulin sensitivity, systolic blood pressure, diastolic blood pressure, C-reactive protein), ***, ; · Change in *** of *** and from screening to *** and ***, *** ; · Change from baseline in medication number and ***. The difference dosages for medications to treat cardiovascular or metabolic co-morbidities; · Difference between *** and *** groups in the rate of progression to type 2 diabetes will be calculated. (subjects non-diabetic at screening); and · Baseline adjusted change in Framingham 10-year risk scores will be calculated and compared between groups score at weeks 28 and 56. ; · Change from *** to *** and *** in BMI between baseline and week 28 and end of treatment (Visit 17, week 56) will be evaluated. Additionally, body composition will be [assessed by *** at ***. These evaluations will be made at ***, and at *** and ***]. The change in weight loss (absolute, percent, absolute, percent of subjects achieving weight loss of > 5% and > 10% of starting weight), waist circumference and obesity associated risk factors will also be assessed over time. Subgroup analyses, including but not limited to analysis by gender, age and race, may be performed. Safety evaluations will include assessment of adverse events, including eye symptoms, ***. *** will also be obtained, and effects of various cofactors including (but not limited to) ***, gender, race, ***, and age will be evaluated. ***.
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