【正文】 .............................................................. 21 Visit 9 (Week 6 End of Study/Early Termination) ..................................................... 21 Visit 10 (Week 6 End of Study/Early Termination) ................................................. 21 Clinical Assessment .................................................................................................... 23 12lead Electrocardiogram .................................................................................... 23 Physical Examination........................................................................................... 23 Pregnancy Test and .............................................................................................. 23 Laboratory Assessments ....................................................................................... 23 Office Blood Pressure and ABPM Measurements .................................................... 24 Safety Assessment ...................................................................................................... 25 Confidential Page 4 of 35 Protocol: ABC01 Final Adverse Event and AE reporting ............................................................................ 25 Statistical Consideration and Analysis ......................................................................... 26 General Statistical Method .................................................................................. 26 Analysis Population............................................................................................ 26 Subject Disposition ............................................................................................ 26 Demographic and Baseline Characteristics ............................................................ 26 Protocol Deviation ............................................................................................. 27 Efficacy Analysis ............................................................................................... 27 Safety Analysis .................................................................................................. 27 Sample Size Estimation/Justification .................................................................... 27 Ethics ...................................................................................................................... 28 Data Handling and Record Keeping ............................................................................ 29 Financing and Insurance ............................................................................................ 30 Publication Policy ..................................................................................................... 31 Reference List .......................................................................................................... 32 APPENDIX A Schedule of Study Evaluations ................................................................. 33 APPENDIX B Blood Pressure Measurement: Office and Ambulatory Blood Pressure Monitoring...................................................................................................................................... 34 Confidential Page 5 of 35 Protocol: ABC01 Final List of Abbreviations Ambulatory Blood Pressure Monitoring ABPM Adverse Event AE Blood Pressure BP Case Report Form CRF Diastolic Blood Pressure DBP Eelectrocardiogram ECG Last observation carried forward LOCF Systolic Blood Pressure SBP … … Confidential Page 6 of 35 Protocol: ABC01 Final 1. PROTOCOL SYNOPSIS Protocol Number: ABC01 Title: A MultiCenter, Randomized, DoubleBlind, PlaceboControlled Study Comparing the Safety and Effectiveness of Drug A 20 mg Once Daily Versus Placebo Using 24Hour Ambulatory Blood Pressure Monitoring (ABPM) In Patients with Mild to Moderate Hypertension. Indication: Mild to moderate hypertension. Objectives: 1. The primary objective of the study is to pare the antihypertensive effectiveness using change from Baseline in mean seated office cuff diastolic blood pressure of Drug A 20 mg once daily to placebo. 2. The secondary objective is to evaluate the safety of lowdose Drug A pared to placebo and change from Baseline at Week 6 or end of study in mean 24hour and mean daytime ambulatory Diastolic Blood Presssure (from time of dosing until 8:00PM) as measured by ABPM. Study Design: The study will employ a randomized, doubleblind design in patients with mild to moderate hypertension. The study includes a 3 to 4week singleblind placebo runin phase and a 6week doubleblind treatment phase. Treatments: All patients will receive placebo tablets once daily for 3 – 4 weeks during the singleblind, runin phase. During the doubleblind treatment phase, patients will be randomized in a 1:1 ratio to receive either Drug A 20 mg or placebo tablets once daily for 6 weeks. Procedures/Visits: Study visits will be scheduled to fit within the window for trough blood pressure (BP) measurements (., prior to next dose and between 22–26 hours after previous dose [24177。2 hours]). Study Population: Approximately 300 patients at approximately 10 sites will be enrolled into the placebo runin phase. It is expected that 20% of patients will not qualify for randomization based on office BP entry criteria and an additional 25% of patients will not qualify based on ABPM entry criteria. The study will randomize approximately 180 patients into the doubleblind treatment. The study population will include males and females ≥ 18 years of age with mild to moderate hypertension (defined as a seated diastolic blood pressure (DBP) ≥ 95 mmHg and ≤ 110 mmHg). Efficacy Measures: Primary Endpoint: The primary efficacy endpoint is the change