【導(dǎo)讀】ProtocolTitleMulti-Center,Randomized,Double-Blind,Placebo-ControlledStudy. AMulti-Center,Randomized,Double-Blind,Placebo-ControlledStudy

　　

【正文】 atients who have insulindependent or uncontrolled Diabetes Mellitus (glycosolated hemoglobin 9%) or hypoglycemia. 3. Systolic blood pressure 179 mmHg either at the screening visit or at the end of the singleblind placebo runin phase of the study as measured by “office” cuff pressure. 4. Difference 10 mmHg in office measured mean diastolic blood pressures between any two Confidential Page 15 of 35 Protocol: ABC01 Final office visits during the runin phase of the study. 5. Patients who have hypertension secondary to a disease or condition or who have a history of malignant hypertension including retinal hemorrhages, exudates and papilledema. 6. Patients who have an AV block greater than first degree including sick sinus syndrome. 7. Patients who have chronic atrial fibrillation or recurrent tachyarrhythmia 8. Patients who have significant bradycardia defined as a resting heart rate 50 beats per minute (bpm). 9. Patients who have clinically significant aortic or mitral valve disease. 10. Patients with target an damage or clinical cardiovascular disease that would preclude their safe inclusion in a placebocontrolled trial. This would include unstable angina pectoris, previous myocardial infarction or CVA in the last 6 months, congestive heart failure, transient ischemic attack (TIA). 11. Patients who have severe peripheral vascular disease 12. Patients with significant thyroid, renal or hepatic disease [TSH times upper limit of normal, urine protein 1+, creatinine mg/dL, AST (SGOT) and/or ALT (SGPT) greater than twice the upper limit of normal]. 13. Patients who perform alternate shift or night work 14. Patients with arm circumference 42 cm (ABPM Cuff) 15. Patients with any history of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid in the past year, or any history of drug abuse or addiction in the past year. 16. Patients who have a history or presence of bronchospastic disease (., asthma, chronic obstructive pulmonary disorder [COPD]). 17. Women who are pregnant or breastfeeding, or who are not using or are not willing to use a medically accepted method of birth control. 18. Patients who have received an investigational drug or device within a period of 30 days prior to enrollment (Visit 2) in the study. 19. Patients who require concurrent use of prohibited prescription (Rx) or overthecounter (OTC) medications. 20. Patients who have previously participated in a study of the Sponsor’s metoprolol tartrate ER tablets. 21. Patients who, in the opinion of the Investigator, have any other medical condition which renders the patient unable to plete the study or which would interfere with optimal participation in the study or produce significant risk to the patient. 22. Patients participating in or planning to enroll in a weight reduction program during the time of the study Confidential Page 16 of 35 Protocol: ABC01 Final Investigational Medicine Products Study Treatment Study Treatment Administration 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. Interruption of Study Treatment Interruption of treatment is not permitted. The dosage cannot be reduced, and, if a patient cannot tolerate the dose, he or she will be discontinued from the study. Study Treatment Compliance The investigational medication will be counted to assess pliance at each visit. Patients who take = 80% of the prescribed doses will be considered pliant. Patients who fall below this threshold will be counseled and reinstructed on dosing procedures. If a patient is chronically nonpliant (. takes 80% of prescribed dose at two consecutive visits), the patient will be asked to terminate from the study. Medication pliance will be recorded on the CRF for each visit. Conitant Medications and Prohibited Medications Allowed Medications Patients will be allowed to take acetaminophen, antacids, lowdose aspirin or nonsteroidal antiinflammatory drug (NSAID) therapy, hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitors, antibiotics, and other drugs considered medically necessary by the Investigator. Prohibited Medications Prohibited medications include the following: ? All antihypertensive drugs。 nitrates or other vasodilators。 betablockers (including ophthalmic)。 are prohibited prior to entry into the singleblind runin phase ? MAO Inhibitors ? Theophylline or betaagonists ? Steroids, not including topical steriods ? Bile acidbinding resins。 ? Highdose NSAID or aspirin therapy (defined as doses required treating arthritis) ? Herbal, Rx, OTC, and/or dietary supplements containing ephedra and other sympathomimetic amines Confidential Page 17 of 35 Protocol: ABC01 Final ? Potassium supplements ? Investigational drugs (beginning 30 days prior to enrollment and continuing through the duration of the trial) Restricted Medications ? Total daily dose of aspirin cannot exceed 162 mg. ? Use of decongestants and antihistamines containing decongestants within two (2) days before any visit is prohibited. ? Use of Selective Serotonin Reuptake Inhibitors (SSRI) is permitted if the patient is on a stable dose of the SSRI for at least three (3) months prior to Screening, is known to be pliant with his/her medication, and agrees to maintain their current stable dose of the SSRI for the duration of the study ? Use of Tricyclic antidepressants (TCA) is permitted if the patient is on a stable dose of the TCA for at least three (3) months prior to Screening, is known to be pliant with his/her medication,