A phase 3 trial of brexpiprazole once-weekly (QW) formulation in patients with acute schizophrenia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Otsuka Pharmaceutical Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

1 Jul 2024 → ongoing

Decision date (initial)

2023-03-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Otsuka Pharmaceutical Co. Ltd

External identifiers

EU CT number

2022-500583-36-00

ClinicalTrials.gov

NCT05325645

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Therapy

To confirm the efficacy of the brexpiprazole QW formulation versus placebo for acute symptoms of schizophrenia

Secondary objectives 1

1. To evaluate the safety of the brexpiprazole QW formulation versus placebo in patients with acute schizophrenia

Conditions and MedDRA coding

Acute Schizophrenia

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Pharmaceuticals And Medical Devices Agency

EMA paediatric investigation plan (PIP)

EMEA-001185-PIP01-11

Plan to share IPD

Yes

IPD plan description

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. Small studies with less than 25 participants are excluded from data sharing. 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 supported by the protocol, statistical analysis plan (SAP) and clinical study report (CSR) on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients at least 18 years of age and below the age of 75 at the time of informed
2. Patients with a diagnosis of schizophrenia based on DSM-5® (295.90) (multiple episodes, currently in acute episode) and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) at the time of informed consent
3. Patients who are hospitalized, or judged to require hospitalization, for acute relapse of schizophrenia at the time of informed consent
4. Patients whose current episode developed within 2 months prior to screening
5. Patients with acute exacerbation of psychotic symptoms and a marked decline in daily functioning who meet all of the following criteria when the placebo administration period begins: (a) PANSS total score of ≥ 70 (b) Scores of ≥ 4 (moderate) for at least 2 of 4 PANSS items (Hallucinatory Behavior, Unusual Thought Content, Conceptual Disorganization, Suspiciousness/Persecution) (c) CGI-S score of ≥ 4 (moderately ill)
6. Patients who were treated with antipsychotics at appropriate doses (recommended doses for the treatment of schizophrenia indicated in the package insert of the drug provided by the manufacturer/distributor) for appropriate durations (at least 6 weeks) and who are considered to have responded to the antipsychotics (excluding clozapine) within 12 months prior to informed consent
7. Patients who experienced a recurrence or exacerbation of symptoms during an antipsychotic-free period (excluding the current episode)
8. Patients who are able to provide written informed consent prior to initiation of any trial-related procedures

Exclusion criteria 13

1. Patients presenting a first episode of schizophrenia based on the clinical judgment of the investigator
2. Patients who are considered resistant/refractory to antipsychotic treatment. Patients who are “unresponsive to medication with 2 or more antipsychotics at effective doses for a sufficiently long duration (6 weeks)” will be deemed resistant/refractory to antipsychotic treatment.
3. Patients who have a history of treatment with clozapine for schizophrenia
4. Patients experiencing acute depressive symptoms within 30 days prior to informed consent that, in the judgment of the investigator, require treatment with an antidepressant
5. Patients who fall under any of the following criteria regarding suicidal ideation and suicidal behavior. • Patients who answered “yes” to Question 4 “Active Suicidal Ideation with Some Intent to Act, without Specific Plan” or Question 5 “Active Suicidal Ideation with Specific Plan and Intent” regarding C-SSRS suicidal ideation at screening (for the past 6 months) or at baseline (since the last assessment) • Patients who exhibited suicidal behavior on C-SSRS at screening (for the past 2 years) or at baseline (since the last assessment) • Patients who present a serious risk of suicide based on the judgment of the investigator
6. Patients presenting tardive dyskinesia at the time of informed consent, as determined by a score of 3 (moderate) or 4 (severe) for Item 8 (severity of abnormal movements) of the AIMS at screening or at baseline
7. Patients with a score of 5 (severe akathisia) in the BARS global clinical assessment of akathisia at screening or at baseline
8. Patients who meet either of the following criteria between 30 days before screening and the start of screening (a) Received 2 or more antipsychotics, each at doses equivalent to ≥ 600 mg/day of chlorpromazine (b) Received a mean daily dose equivalent to > 800 mg/day*,** of chlorpromazine *If multiple antipsychotics are taken in the same day, this is to be the combined equivalent dose. **This does not include administration of antipsychotic medication at doses equivalent to less than 100 mg/day of chlorpromazine, which are not expected to have any antipsychotic effect. Chlorpromazine equivalent doses are based on Equivalent Conversion Table for Antipsychotics, as specified separately.
9. Patients with a diagnosis of a concurrent mental disorder besides schizophrenia (schizoaffective disorder, major depressive disorder, bipolar I disorder, bipolar II disorder, general anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, dementia or mild neurocognitive disorder, personality disorder, etc) based on DSM-5®. However, this exclusion does not apply to the following: • Caffeine- or tobacco-related disorders
10. Patients who have met the DSM-5® diagnostic criteria for substance-related or addictive disorder, including alcohol and benzodiazepines but excluding caffeine and tobacco, within 180 days before commencement of investigational medicinal product (IMP) administration
11. Patients who have a clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorder. Medical conditions that are minor or well-controlled may be considered acceptable if the condition does not interfere with safety and efficacy assessments.
12. Patients with known hypersensitivity or intolerance to brexpiprazole or patients with confirmed resistance to brexpiprazole therapy. Patients who have received brexpiprazole to treat the current episode.
13. Patients judged by the investigator to be unsuitable for participation in the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy endpoint: Mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Otsuka Pharmaceutical Co. Ltd.

Sponsor organisation

Otsuka Pharmaceutical Co. Ltd.

Address

2 9 Kanda Tsukasamachi, Chiyodo Ku Chiyodo Ku

City

Tokyo

Postcode

101-0048

Country

Japan

Scientific contact point

Organisation

Otsuka Pharmaceutical Co. Ltd.

Contact name

EU Clinical Trials Helpdesk

Public contact point

Organisation

Otsuka Pharmaceutical Co. Ltd.

Contact name

EU Clinical Trials Helpdesk

Third parties 14

Sponsor responsibilities

Article 77 compliance

Otsuka Pharmaceutical Co. Ltd.

Article 77 implementation

Otsuka Pharmaceutical Co. Ltd.

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications