Ateeq Ahmad1, Saifuddin Sheikh1, Mujtaba Ali Khan2, Alok Chaturvedi2, Piyush Patel2, Ronak Patel3, Bakul Chandrakant Buch4, Rajendra Someshwar Anand5, Timirkumar Chandrakant Shah6, Vaishal Nareshchandra Vora7, Vikhram Ramasubramanian8, Satyanarayana Rao9, Narendra Kumar10, B S V Prasad11, Ramanathan Sathianathan12, Kamal Kumar Verma13, Venu Gopal Jhanwar14, Nand Kumar15, Sandip Shah16, Pronob Kumar Dalal17, Brahmdeep Sindhu18, Payel Talukdar19, Imran Ahmad1. 1. Jina Pharmaceuticals Inc, Libertyville, IL, USA. 2. Intas Pharmaceuticals Ltd, Ahmedabad, Gujarat, India. 3. Lambda Therapeutic Research Ltd, Ahmedabad, Gujarat, India. 4. Shri Hatkesh Healthcare Foundation, Junagadh, Gujarat, India. 5. Kanoria Hospital and Research Centre, Gandhinagar, Gujarat, India. 6. Divyam Hospital, Surat, Gujarat, India. 7. Ratandeep Multispecialty Hospital, Ahmedabad, Gujarat, India. 8. Ahana Hospitals, Madurai, Tamil Nadu, India. 9. JSS Medical College Hospital, Mysore, Karnataka, India. 10. Mysore Medical College and Research Institute, K.R. Hospital, Mysore, Karnataka, India. 11. Sujata Birla Hospital and Medical Research Center, Nasik, Maharashtra, India. 12. Sri Ramachandra Medical College and Research Institute, Chennai Tamil Nadu, India. 13. S.P. Medical College and A.G. Hospitals, Bikaner, Rajasthan, India. 14. Deva Institute of Healthcare and Research, Varanasi, Uttar Pradesh, India. 15. All India Institute of Medical Sciences, New Delhi, India. 16. Gujarat Medical Education & Research Society Medical College, Gotri, Vadodara, India. 17. King George's Medical University, G.M. Associated Hospitals, Lucknow, Uttar Pradesh, India. 18. Civil Hospital, Gurugram, Haryana, India. 19. Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India.
Abstract
OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.
OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.