Date

2021-12-08

Protocol

Protocol changed

Item Changed

Intervention(s) planned

Previous Version

•Study setting: Colombo North Teaching Hospital This is a 46-week, open-label, multi-center, extension to study NW-3509/014/II/2019 designed to evaluate the long-term safety, tolerability and preliminary efficacy of evenamide as add-on treatment in patients with treatment resistant schizophrenia on a stable therapeutic dose of an antipsychotic. In Study 014, 50 patients are to be randomized equally (1:1) to the 7.5 mg bid and 15 mg bid doses (approximately 25 in each group), and key safety data from these patients will be reviewed by an Independent Safety Monitoring Board (ISMB). If this review of the data indicates there are no safety issues, the 30 mg bid dose group will be initiated, and randomization will continue, with a total of approximately 50 patients being enrolled in each of the three treatment groups. If the 30 mg bid group is not added, the 150 patients will be randomly assigned (1:1) to the 7.5 and 15 mg bid treatment groups (approximately 75 in each group). Intervention NW3509 Fixed oral doses of 30 mg BID orally for 46 weeks therapy of NW-3509 (Evenamide)

Next Version

This is a 46-week, open-label, multi-center, extension to Study NW-3509/014/II/2019 (Study 014) designed to evaluate the long-term safety, tolerability and preliminary efficacy of evenamide as add-on treatment in patients with TRS on a stable therapeutic dose of an antipsychotic. In Study 014, after 50 patients were randomized equally (1:1) to the 7.5 mg bid (n=26) and 15 mg bid doses (n=24) and completed their participation in the study, key safety data from these patients were reviewed by an Independent Safety Monitoring Board (ISMB). This review of the data indicated that there were no safety issues, therefore, the 30 mg bid dose group was initiated, and randomization was continued, with patients being randomized 1:1:2 to doses of 7.5, 15 and 30 mg bid. Subsequently, the Study 014 protocol was amended to discontinue the 7.5 mg bid dose group, and to randomize patients 1:3 to doses of 15 mg bid and 30 mg bid, respectively. Patients randomized to participate in Study 014 who complete 6 weeks of open-label treatment, are not experiencing moderate/severe side effects, have not shown severe worsening of their symptoms of schizophrenia, and who meet other entry criteria for this study will be eligible to receive evenamide in this open-label extension study (Study 015) for 46 weeks, for a total treatment period with evenamide of up to 52 weeks. The duration of this extension study may be increased, contingent on the availability of data from other studies to support the additional treatment. Patients randomized to doses of 15 mg bid or 30 mg bid in Study 014 will continue in Study 015 on the same dose of evenamide they were receiving on the last day (Day 43) of the prior study, while patients randomized to the 7.5 mg bid dose in Study 014 will have their dose increased to 15 mg bid upon entry into Study 015. Patients already enrolled in Study 015 at the 7.5 mg bid dose will have their dose increased to 15 mg bid at their next scheduled clinic visit. Dose reductions to once daily dosing may be performed at any time if intolerance develops.