Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients

Exclusion Criteria

• •1. Newly diagnosed patients and not having any suitable treatment exposure in the past for their bipolar mood disorder.
• •2. \> 20% improvement in YMRS total scores between screening and randomization visits.
• •3. Patients who meet DSM-5 criteria for any psychiatric disorder other than Bipolar I Disorder with Acute Mania Episode with or without mixed features.
• •4. Patients with seizure disorder.
• •5. Obsessive compulsive disorder or any other co-morbid Axis I anxiety disorder
• •6. Patients with borderline or anti-social personality disorder of sufficient current severity to interfere with conduct of the study
• •7. Patients with classical premenopausal symptoms found at risk of developing intolerable hot flushes, irregular vaginal bleeding.
• •8. Use of the following medications:
• •* Antihypertensive agents if stable dose has not been administered for at least 1 month before randomization
• •* Antidepressants in the week (or a period of 5 half-lives of the drug) prior to randomization
• •* Continuous daily or standing orders use of benzodiazepines during the month preceding screening (approximately 5 weeks prior to screening)
• •* Potent cytochrome P450 (CYP) inducers and CYP2D6/CYP3A4 inhibitors 14 days prior to randomization
• •* Depot antipsychotic medications within 1 dosing interval prior to randomization
• •* Use of systemic estrogens 6 weeks prior to randomization
• •* Patients currently on carbapenem agents
• •9. Any of the following laboratory abnormalities
• •* Serum bilirubin ≥ 1.5 times ULN
• •* Serum AST/ALT ≥ 2.5 times ULN
• •* Serum TSH \>10% above the ULN, regardless of treatment for hypothyroidism or hyperthyroidism
• •* Serum triglyceride level \> 2.5 times ULN
• •10. Patients with the following cardiac conditions are excluded:
• •* Recent myocardial infarction (\<12 months)
• •* QTc prolongation (screening electrocardiogram with QTc \>450 msec for men, QTc\> 470 msec for women)
• •* History of QTc prolongation or using concomitant medications (as judged by the Investigator) which prolong QTc interval
• •* Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia
• •* De compensatory congestive heart failure
• •* Complete left bundle branch block
• •* First-degree heart block with PR interval \> 0.22 seconds
• •11. Presence of a coagulation disorder; active or past history of venous thromboembolism including deep venous thrombosis or pulmonary embolism.
• •12. Current prolonged immobilization.
• •13. History or current presence of retinal pathology including retinal vein thrombosis
• •14. Increased risk of stroke as per the Investigator's discretion.
• •15. History of hypersensitivity or intolerance to tamoxifen or any other ingredients of the preparation.
• •16. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease as per history and medical examination.
• •17. Drug screen positive for any drug of abuse at screening (with the exception of benzodiazepines used in therapeutic dose for management of acute mania), active substance abuse in the past 2 months or history of substance dependence (excluding nicotine and caffeine) within 3 months of screening.
• •18. History of breast or uterine cancer, or abnormal uterine bleeding.
• •19. Current leukopenia or thrombocytopenia as judged by the Investigator in the best health interest of the subject.
• •20. Clinically significant suicidal or homicidal ideation.
• •21. Participation in a clinical trial of another investigational drug within 30 days prior to screening.