dm+d

Unassigned

New Medicines

RxultiMajor depressive disorder in adults

Information

Rxulti
New molecular entity
Ostuka
Ostuka

Development and Regulatory status

None
Phase III Clinical Trials
Launched
Jun 21Still showing as PIII in Europe in company pipeline [20].
Jun 20Remains PIII in Europe in Otsuka pipeline [19].
Mar 19Still PIII in EU in Otsuka pipeline [18].
Dec 17Still listed as in PIII development in company pipeline [17].
Dec 17Was launched in US in Aug 2015 [16].
Sep 16PIII development continues in EU [14].
Sep 15PIII development continues in EU [13].
Jul 15US FDA approves REXULTI® (Brexpiprazole) as an adjunctive treatment for adults with Major Depressive Disorder. It is expected to become available to patients in the U.S. in early August 2015 [12].
Jul 14Filed in the US for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder [8].
Jun 11PIII programme starts [1].

Category

Dopamine partial agonist. Tablet formulation.
Annually, 5% of adults have an episode of depression. About one in four women and one in ten men will develop depression severe enough to require treatment at some time in their lives. Most depressive states are at the mild-to-moderate end of the spectrum and it is these that are mainly seen in primary care. [9]
Major depressive disorder in adults
Oral

Trial or other data

Apr 21A PIII trial assess the safety, efficacy and tolerability of brexpiprazole as adjunctive maintenance therapy to protocol-specific open-label antidepressant therapy is recruiting (NCT03538691). The trial started in Jul 18 and is recruiting 1,450 adults in the US. Primary outcome is time-to-relapse; collection of these data is due to complete Sep 22 [21].
Dec 14Results from two PIII studies of brexpiprazole as adjunctive treatment in major depressive disorder not adequately responding to antidepressant monotherapy show greater improvement than adjunctive placebo in MADRS total score at Week 6 in the efficacy population per final protocol in Study 1 (2mg+ADT [N=175]: -3.21, p=0.0002), and in Study 2 (1mg+ADT [N=211]: -1.30, p=0.0737; 3mg+ADT [N=213]: -1.95, p=0.0079). Similar results were observed for the efficacy population in both studies. The completion rate was high (>90%) and comparable across brexpiprazole and placebo groups. Discontinuations due to adverse events were low across all groups (1mg = 1.3%, 2mg = 3.2%, 3mg = 3.5%, placebo = 0.7%) and only one patient discontinued due to lack of efficacy (in the brexpiprazole 1mg group). All doses of adjunctive brexpiprazole resulted in notably low levels of sedating or activating side effects [11].
Jan 14Results from the PIII Pyxis trial, a multicenter, randomized, placebo-controlled study in the US, Europe and Canada, showed statistically significant improvements in average Montgomery-Åsberg Depression Rating Scale totals in patients treated with brexpiprazole vs placebo. The drug also demonstrated a statistically significant advantage for all secondary outcome measures of change in the Sheehan Disability Scale to week 14 of treatment [8].
Dec 13NCT02013531 Protocol 331-13-002: is an exploratory PIII, multicentre, open-label, flexible-dose trial of brexpiprazole as an adjunctive treatment in 50 adults with major depressive disorder and anxiety symptoms. The primary outcome is change from baseline in MADRS Total Score to Week 6. The study starts Nov 13 and is due to complete Oct 14 [7].
Dec 13NCT02013609 Protocol 331-13-003: is an PIII exploratory, multicentre, open-label, flexible-dose trial of brexpiprazole as an adjunctive treatment in 50 active adults, 18 to 30 years old, with major depressive disorder who are in a school or work environment. The primary outcome is change from baseline in MADRS Total Score to Week 12. The study starts Nov 13 and is due to complete Oct 14 [7].
Dec 13NCT02012218 A PIIIb multicenter, open-label exploratory trial to evaluate the efficacy, safety, and subject satisfaction with brexpiprazole as adjunctive therapy in the treatment of 80 adults with major depressive disorder and an inadequate response to previous adjunctive therapy. The primary outcome is change from baseline to week 6 in the MADRS total score. The study starts Nov 13 and is due to complete Oct 14 [6].
Nov 13NCT01987960 is a PIII randomised, double-blind, placebo-controlled, flexible-dose study of brexpiprazole as adjunctive treatment to paroxetine or sertraline in 592 adult patients suffering from post-traumatic stress disorder (PTSD). The primary outcome is change in PTSD symptoms using CAPS-2 total score from baseline to week 28. The study starts Nov 13 and is due to complete Aug 15 [5].
Sep 13NCT01944969 is a PIII, open-label, long-term extension study to evaluate the safety and tolerability of brexpiprazole as adjunctive treatment in 1184 patients with major depressive disorder. The study starts Sep 13 and is due to complete Nov 16 [4].
Sep 13NCT01942733 is a PIII, open-label, flexible-dose, exploratory study of brexpiprazole as adjunctive treatment of sleep disturbances in 50 patients with major depressive disorder. Primary outcomes measured at week 8 include polysomnographi and actigraphy parameters, and subjective parameters using a sleep diary. The study starts Sep 13 and is due to complete Jun 14 [4].
Sep 13NCT01942785 is a PIII, open-label, flexible-dose, exploratory study of brexpiprazole as adjunctive treatment of irritability in 50 patients with major depressive disorder and an inadequate response to antidepressant therapy. The primary endpoints include scores on the following assessments measured from baseline to week 6: Kellner Symptom Questionnaire (KSQ), KSQ anger-hostility subscore, Barratt Impulsiveness Scale, Version 11 (BIS-11), Anger Attacks Questionnaire (AAQ). The study starts Sep 13 and is due to complete Apr 14 [4].
Apr 13NCT01838681 is a PIII, randomised, double-blind study of 1 to 3 mg/day of brexpiprazole vs placebo as adjunctive treatment in 1462 patients with major depressive disorder with an inadequate response to antidepressant treatment. The primary outcome is full remission (based on theMontgomery and Åsberg Depression Rating Scale (MADRS) total score) over the treatment period of 36 weeks. The study starts May 13 and is due to complete Nov 15.
Nov 11Lundbeck and Otsuka are collaborating on a number of pipeline agents including OPC-34712 [2].
Jun 11Three PIII studies registered. NCT01360645 (Pyxis): A multicentre, randomized, double-blind trial of fixed dose OPC-34712 (2mg) vs placebo as adjunctive therapy in the treatment of 720 adults with major depressive disorder who have demonstrated an incomplete response to a prospective trial of an antidepressant that is continued through this study. The primary outcome is change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization to the end of treatment at Week 14. The study will start in Jul 11 and is due to complete Mar 13. NCT01360632 (Polaris) is of similar design to the above but uses two fixed doses (1 or 3mg) vs placebo and will enrol 1250 adults. The study will start in Jun 11 and is due to complete May 13. NCT01360866 (Orion) is a long-term, open-label trial to evaluate the safety and tolerability of oral OPC-34712 (0.5-3mg) as adjunctive therapy in 1280 patients. The primary outcome is frequency and severity of adverse effects over 52 weeks. The study will start in Oct 11 and is due to complete Feb 14 [1].