A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial

To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.

Time frame: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment.

Time frame: Phase B week 6 (14/16 weeks after randomization).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.

Time frame: Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14)

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse).

Time frame: From randomization to Phase B week 6 (14/16 weeks after randomization).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for CGI-S score and CGI-I score in Phase B.

MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment.

Time frame: Phase B week 6 (14/16 weeks after randomization).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.

To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables.

Time frame: From screening (Day -28 to Day-1) upto post treatment follow-up.

Population: Randomized subjects in Phase B who received at least one dose of double-blind trial medication as indicated on the dosing record.

MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment.

Time frame: Phase B week 6 (14/16 weeks after randomization).

Population: Number of subjects in the Safety Sample who had an end of Phase A (ie, Week 8 or 10) value and at least one post randomization efficacy evaluation for MADRS Total Score in Phase B.

To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.

Time frame: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for SDS Score in Phase B.

To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe).

Time frame: Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).

Population: All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.