The study consists of 2 periods and 4 visits (V): a run-in period of at least 4 weeks (V1 to V2) and a 12-week perindopril treatment period (V2 to V4).
After written informed consent, patients will undergo screening evaluations (V1). Patients who meet the selection criteria will enter a run-in period of 4 weeks where they will be given dietary and exercise counseling as standardized non-drug therapy. After the run-in period (V2), patients will start the pharmacological therapy period where they will receive perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-drug therapy.
During the 12-week pharmacological treatment, patients will attend an intermediate study visit (V3) at approximately 6 weeks and a final visit (V4) for efficacy and safety assessments.
Body weight, body mass index (BMI), waist and hip circumference, and body fat mass estimation will be assessed at every study visit.
A total of 160 subjects will be enrolled, to have approximately 120 subjects evaluable.
After V2, patients will be administered perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-pharmacological therapy.
Blood sampling for clinical safety laboratory assessments (hematology and plasma biochemistry) will be collected at the screening, at the end of the run-in period, at the intermediate treatment visit, and at the end of the perindopril treatment period.
At the screening, blood will also be collected for CPD genotyping, but the results will remain blinded until database closure.
Safety will be evaluated through the assessment of treatment-emergent adverse events, vital signs and clinical laboratory tests. Adverse events will be monitored throughout the study. Vital signs will be recorded at each scheduled visit. Clinical safety laboratory parameters will be collected at screening, end of the run-in period, at the intermediate treatment visit, and at the end of the treatment period.
Abnormalities in vital signs and laboratory parameters will be assessed by the clinical investigator in terms of clinical relevance. Clinically significant abnormalities in clinical laboratory and vital signs will be reported as adverse events.
Associations between CPD SNPs genotypes and patient response will be assessed through the appropriate statistical methods. The primary efficacy analysis will compare the response rate in the group of subjects with the SNPs of interest and the group of the remaining subjects. A logistic regression model will be used to assess the group differences. Weight and fat mass at the start of the perindopril treatment period and gender will be used as covariates. Other covariates will be investigated for exploratory purposes, but will not be included in the model where main treatment effects are tested and compared. All the secondary efficacy endpoints will be assessed using analysis of covariance (ANCOVA). In general, the principles applied for the primary efficacy analysis will be replicated for the secondary efficacy analysis.
Adverse events will be tabulated and summarized according to system organ class (SOC) and preferred term (PT).
