臨床研究等提出・公開システム

A multi-center, open-label trial to assess the long-term safety and efficacy of brexpiprazole as adjunctive therapy in patients with major depressive disorder

A Long-Term Study of Brexpiprazole in Patients With Major Depressive Disorder

248

The total brexpiprazole population (247 subjects), by sex, comprised 59.1% male subjects (146 subjects) and 40.9% female subjects (101 subjects), and the population age (mean ± standard deviation, same below) was 44.4 ± 13.9 years (range: 22 to 80 years). Newly enrolled subjects (31 subjects), by sex, comprised 41.9% male subjects (13 subjects) and 58.1% female subjects (18 subjects), and the population age was 70.3 ± 4.5 years (range: 65 to 80 years). Rollover subjects (216 subjects) by sex, comprised 61.6% male subjects (133 subjects) and 38.4% female subjects (83 subjects), and the population age was 40.7 ± 10.3 years (range: 22 to 64 years).

Of the 247 subjects included in the safety analysis set (216 rollover subjects, 31 newly enrolled subjects), 55.9% (138 subjects [132 rollover subjects, 6 newly enrolled subjects]) completed the trial and 44.1% (109 subjects [84 rollover subjects, 25 newly enrolled subjects]) discontinued the trial.The main reasons for withdrawals were adverse events in 66 subjects (48 rollover subjects, 18 newly enrolled subjects) and withdrawal of consent in 25 subjects (20 rollover subjects, 5 newly enrolled subjects).

The incidence of adverse events was 93.5% (231/247 subjects) among the total brexpiprazole treatment population and 96% (30/31 subjects) among newly enrolled subjects. Adverse events occurring in 5% or more of the total brexpiprazole treatment population were weight gain (33.2% [82 subjects]), akathisia (23.5% [58 subjects]), nasopharyngitis (21.1% [52 subjects]), somnolence (10.5% [26 subjects]), insomnia (9.7% [24 subjects]), headache (9.3% [23 subjects]), tremor (8.5% [21 subjects]), increased appetite (7.3% [18 subjects]), extrapyramidal disorder (6.5% [16 subjects]), malaise (6.1% [15 subjects]), constipation, and major depression (5.7% [14 subjects] each). Adverse events occurring in 10% or more of the newly enrolled subjects were akathisia (38.7% [12 subjects]), tremor (19.4% [6 subjects]), nasopharyngitis (16.1% [6 subjects]), weight gain, dyskinesia, extrapyramidal disorder, and major depression (12.9% [4 subjects] each). Both among the total brexpiprazole treatment population and the newly enrolled subjects, most of the adverse events and adverse reactions that occurred were mild or moderate. - There was 1 death, a 49-year-old man who was a rollover subject from one of the brexpiprazole groups of the preceding trial. The name of the serious adverse event was “death.” The event occurred after conclusion of IMP administration (date of occurrence unknown) and was judged as not related to the IMP. - The incidences of serious adverse events were 3.6% (9/247 subjects) for brexpiprazole overall and 3.2% (1/31 subjects) among newly enrolled subjects. There were no serious adverse events that occurred in more than 1 subject, and the only serious adverse events judged to be related to the IMP were dyskinesia in 1 rollover subject continuing from the placebo group of the previous trial and major depression in 1 newly enrolled subject (0.4% [1/247] each). - The incidences of adverse events leading to discontinuation were 26.7% (66/247 subjects) for brexpiprazole overall and 58.1% (18/31 subjects) among newly enrolled subjects.

Refer to "adverse events"

- As reductions in MADRS total score, CGI-S, HAM-D17-item total score, and mean SDS score from the baseline values throughout the administration period were seen among the total brexpiprazole treatment population, this demonstrated sustained improvement of symptoms by long-term administration of brexpiprazole. Similar results were observed among the newly enrolled subjects (subjects aged 65 years or older), with reductions from baseline observed for all endpoints. - Both among the total brexpiprazole treatment population and among newly enrolled subjects, MADRS response rate, MADRS remission rate, and CGI-I improvement rate were sustained throughout the treatment period.

Brexpiprazole at 2 mg/day for up to 52 weeks achieved sustained improvement in the efficacy endpoints (mean change in MADRS total score, etc.), demonstrating long-term efficacy as adjunctive therapy in patients with major depressive disorder who show inadequate response to monotherapy with commercially available antidepressants (SSRIs or SNRIs for rollover subjects and SSRIs, SNRIs, or mirtazapine for newly enrolled subjects). There were no major safety concerns and tolerability was favorable.

July. 31, 2023

Yes

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Supporting Materials: Study Protocol and Statistical Analysis Plan (SAP) Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data. Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.

Matsumaru Takehisa

Otsuka Pharmaceutical Co., LTD.

3-2-27, Otedori, Chuo-ku, Osaka, Japan

CL_OPCJ_RDA_Team@otsuka.jp

Otsuka Pharmaceutical Co., LTD.

2-16-4, Konan, Minato-ku, Tokyo, Japan

+81-3-6361-7314

opc_ctr@otsuka.jp

completed

Oct. 04, 2018

Interventional

A multi-center, open-label trial

treatment purpose

3

Rollover subjects
1) Outpatients
2) Subjects who have completed the double-blind period of the double-blind trial and can commence the treatment period of this trial within 28 days from the completion of the double-blind period of the
double-blind trial
3) Subjects who have a level of comprehension sufficient to
allow them to give written informed consent to all of the
observation/examination/evaluation items specified in the
protocol, and who can understand the contents of the trial
4) Subjects with a DSM-5 classification-based diagnosis of ""major depressive disorder, single episode"" or ""major depressive disorder, recurrent episode""
New subjects
1) Outpatients
2) Male and female patients >= 65 years of age (at the time of informed consent)
3) Subjects who have a level of comprehension sufficient toallow them to give written informed consent to all of the observation/examination/evaluation items specified in the protocol, and who can understand the contents of the trial
4) Patients with a DSM-5 classification-based diagnosis of ""major depressive disorder, single episode"" or ""major depressive disorder, recurrent episode"" whose current episode has persisted for at least 8 weeks

Rollover subjects
1) Female subjects who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at baseline
2) Sexually active male subjects or sexually active female subjects of childbearing potential, who will not agree to practice 2 different methods of birth control or to remain abstinent during the trial and for 30 days after the final IMP administration. For birth control, 2 of the following methods must be used: vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide.
3) Subjects who experience a change to the manic state in the antidepressant treatment period of the double-blind trial
4) Subjects who are discovered to not meet the inclusion criteria or to fall under any of the exclusion criteria in the doubleblind trial
5) Subjects who showed marked noncompliance with the IMP treatment in the double-blind trial (subjects whose IMP compliance rates are < 65% between prescribed visits)
New subjects
1) Sexually active male subjects who will not agree to practice 2different methods of birth control or to remain abstinent during the trial and for 30 days after the final IMP administration. For birth control, 2 of the following methods must be used: vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide.
2) Patients with a treatment history showing that all antidepressants (also including those not used for the current major depressive episode) cannot be tolerated
3) Patients with a history of electroconvulsive therapy
4) Patients with a diagnosis of any of the following diseases according to DSM-5
a) Neurocognitive disorders
b) Schizophrenia spectrum and other psychotic disorders
c) Bipolar and related disorders
d) Feeding and eating disorders
e) Obsessive-compulsive disorder
f) Panic disorder
g) Posttraumatic stress disorder

Both

Major depressive disorder

investigational material(s)
Generic name etc : Brexpiprazole
INN of investigational material : 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one
Therapeutic category code : 117 Psychotropic agents
Dosage and Administration for Investigational material : 2 mg/day(starting dose 1mg/day) of Brexpiprazole will be orally administered once daily


control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

safety
Adverse events, clinical laboratory tests, vital signs (body temperature, diastolic blood pressure and systolic blood pressure and pulse rate [supine, sitting, and standing positions]), physical examination, waist circumference, 12-lead ECG, body weight, body mass index, C-SSRS, DIEPSS, AIMS, BARS

efficacy
Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression -Global Improvement (CGI-I), Clinical Global Impression -Severity of Illness (CGI-S), Hamilton Depression Rating Scale (HAM-D), Sheehan Disability Scale (SDS)

+81-248-23-4401

June. 26, 2018