This Study Tests Whether BI 409306 Prevents Patients With Schizophrenia From Becoming Worse. This Study Looks at How Well Patients Tolerate BI 409306 and How Effective it is Over 6 Months

Schizophrenia Clinical Trial

Official title:

A Phase II Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered BI 409306 During a 28-week Treatment Period as Adjunctive Therapy to Antipsychotic Treatment for the Prevention of Relapse in Patients With Schizophrenia.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03351244
• Other study ID #: 1289-0049
• Secondary ID: 2017-002369-23
• Status: Terminated
• Phase: Phase 2
• Start date: December 7, 2017
• Est. completion date: March 31, 2021

Study information

• Verified date: April 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of the study is to investigate the efficacy, safety and tolerability of BI 409306 once daily compared with placebo given for 28 weeks in patients with schizophrenia on antipsychotic treatment. The study is designed to show superiority of BI 409306 over placebo in preventing relapse of schizophrenia symptoms.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 264
• Est. completion date: March 31, 2021
• Est. primary completion date: March 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) diagnosis of schizophrenia >= one year prior to randomisation.

• Outpatients in the stable phase of illness, as assessed by the investigator after review of medical records or documented discussion with treating clinician.

• Patients currently taking a stable dose of antipsychotic medication(s) for at least 12 weeks prior to randomisation.

• Detectable level of current antipsychotic medication(s) in plasma from blood drawn at Visit 1 (unless no assay is available for the antipsychotic(s) currently prescribed).

• Patients who have experienced at least 2 relapses within the past 5 years or at least 1 relapse if they were diagnosed less than 3 years ago. Relapse is defined as the patient having any of the following using the above number of relapses and time frames:

• Hospitalization for psychosis (involuntary or voluntary admission), intensive outpatient therapy or use of home treatment as an alternative to hospitalization (verified via medical record).

• Emergency Department visit for worsening schizophrenia symptoms (verified via medical record).

• Deliberate self-injury and/or violent behaviour resulting in significant injury to another person or property (verified by police record or treating mental health provider written record or documented phone conversation).

• Change in the patient's antipsychotic medication or increase in antipsychotic medication dosage due to worsening of schizophrenia symptoms (verified by pharmacy records or treating mental health provider written record or documented phone conversation).

• Clinical Global Impressions-Severity (CGI-S) score =4 at Visit 1 and 2.

• Positive and Negative Syndrome Scale (PANSS) total score <80 and a score of = 4 on individual PANSS items conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content at Visit 1.

• Of full age (according to local legislation, usually = 18 years) and = 55 years at the time of informed consent.

• Patients must have an identified informant who will be consistent throughout the study.

• Patients who report living at the same address for the 3 months prior to randomisation.

• Male or female patients.

-- Female patients of childbearing potential must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. Patients must agree to use birth control throughout the trial and for at least 28 days after treatment has ended. Acceptable methods of birth control include combined estrogen-progestin oral, intravaginal or transdermal contraceptives, progestogen-only oral, injectable or implantable contraceptives, intrauterine devices (IUDs), intrauterine hormone releasing systems (IUSs), bilateral tubal occlusion, vasectomized sexual partner, and complete sexual abstinence (if acceptable by local health authorities) is allowed when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

• Male patients who are able to father a child must be ready and able to be abstinent or use adequate contraception for the duration of study participation and for at least 28 days after treatment has ended.

• Signed and dated written informed consent in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. If the patient has a legal representative, then this legal representative must give written informed consent as well.

Exclusion criteria:

• Patients treated with more than two antipsychotic medications (including more than two dosage forms).

• Patients who are currently being treated with clozapine, or who have been treated with clozapine in the past 5 years.

• Patients with a categorical diagnosis of another current major psychiatric disorder per the Mini-international neuropsychiatric Interview (M.I.N.I.).

• Homicidal behaviour (in the investigator's judgement) in the past 2 years.

• Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).

• Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent).

• In the judgment of the investigator, any clinically significant finding from the physical examination or laboratory value deviating from normal or any evidence of a clinically significant concomitant disease or any other clinical condition that would jeopardize a patient's safety while participating in the clinical trial.

• Other known neurological diseases (including but not limited to any kind of seizures or stroke).

• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.

• Planned elective surgery requiring general anesthesia, or hospitalization for more than 1 day during the study period.

• Significant history of drug or alcohol dependence or abuse (Substance Use Disorder as defined in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) or ICD-10) within the last six months prior to informed consent. (Not including caffeine or nicotine).

• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.

• Patients taking strong or moderate CYP1A2 inhibitors who are also a CYP2C19 Poor Metabolizer (PM). Patients taking medication known to be strong or moderate inhibitors of CYP1A2 must be prospectively genotyped to ensure they are not poor metabolizers of CYP2C19. (A list of CYP1A2 and CYP2C19 inhibitors can be found in the Investigator Site File (ISF)).

• Patients taking strong or moderate CYP1A2 inhibitors who are also taking concomitant strong or moderate CYP2C19 inhibitors. (A list of CYP1A2 and CYP2C19 inhibitors can be found in the ISF)

• Patients with a history of moderate to severe hepatic impairment (Child-Pugh B / C).

• Patients with a history of moderate to severe renal impairment (Stage 3 - 5).

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

• In the judgment of the investigator, inability of the patient to comply with the clinical trial procedures.

• Currently enrolled in another investigational device or drug study, or less than 6 months from Visit 1 since ending another investigational device or drug study(s), or participation in > 2 investigational drug clinical trials in the past 2 years.

• Previous randomisation in any BI 409306 study.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• BI 409306
28 week treatment period
• Placebo
28 week treatment period

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Chatham-Kent Clinical Trials Research Centre	Chatham	Ontario
Canada	IUSMM Institut Universitaire en Sante Mentale de Montreal	Montreal	Quebec
Canada	Dr. Alexander McIntyre Inc.	Penticton	British Columbia
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario
Canada	The Medical Arts Health Research Group	Vancouver	British Columbia
France	HOP la Colombière	Montpellier
France	GHU Paris Psychiatrie et Neurosciences	Paris
France	HOP Guillaume Régnier	Rennes
France	HOP Nord	Saint-Priest-en-Jarez
France	HOP Sainte Musse	Toulon
Japan	Fujita Health University Hospital	Aichi, Toyoake
Japan	Okehazama Hospital Fujita Kokoro Care Center	Aichi, Toyoake
Japan	National Center for Global Health and Medicine Kohnodai Hospital	Chiba, Ichikawa
Japan	Fukuoka University Hospital	Fukuoka, Fukuoka
Japan	Kuramitsu Hospital	Fukuoka, Fukuoka
Japan	Soushu Hospital	Kanagawa, Atsugi
Japan	Kishiro Mental Clinic	Kanagawa, Kawasaki
Japan	Nara Medical University Hospital	Nara, Kashihara
Japan	National Hospital Organization Hizen Psychiatric Medical Center	Saga, Kanzaki-gun
Japan	National Center Neurology and Psychiatry	Tokyo, Kodaira
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Taiwan	NCKUH	Tainan
Taiwan	Taoyuan Psychiatric Center	Taoyuan
United States	Michigan Clinical Research Institute PC	Ann Arbor	Michigan
United States	Atlanta Center	Atlanta	Georgia
United States	Community Clinical Research, Inc.	Austin	Texas
United States	Hassman Research Institute	Berlin	New Jersey
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	Alam Medical Research, Inc.	Chicago	Illinois
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Precise Research Centers	Flowood	Mississippi
United States	Collaborative Neuroscience Network, LLC (CNS)	Garden Grove	California
United States	Behavioral Research Specialists, LLC	Glendale	California
United States	MD Clinical	Hallandale Beach	Florida
United States	Reliable Clinical Research	Hialeah	Florida
United States	University Hills Clinical Research	Irving	Texas
United States	Lake Charles Clinical Trials LLC	Lake Charles	Louisiana
United States	Altea Research Institute	Las Vegas	Nevada
United States	Synergy East	Lemon Grove	California
United States	University of California Los Angeles	Los Angeles	California
United States	Meridien Research	Maitland	Florida
United States	Clinical Trials of America, LLC	Monroe	Louisiana
United States	Manhattan Behavioral Medicine PLLC	New York	New York
United States	New York State Psychiatric Institute	New York	New York
United States	Behavioral Clinical Research, Inc.	North Miami	Florida
United States	Excell Research Inc.	Oceanside	California
United States	Orange County Neuropsychiatric Research Center LLC	Orange	California
United States	Meridien Research	Orlando	Florida
United States	Alea Research	Phoenix	Arizona
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	@Health Texas	Richmond	Texas
United States	St. Charles Psychiatric Associates & Midwest Research Group	Saint Charles	Missouri
United States	Arch Clinical Trials	Saint Louis	Missouri
United States	PsychCare Consultants Research	Saint Louis	Missouri
United States	Collaborative Neuroscience Network, LLC (CNS)	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  France,  Japan,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence Rate of First Relapse After 28 Weeks of Treatment	The incidence rate of first relapse after 28 weeks of treatment is reported. For each treatment group, the incidence rate was calculated as the number of events / sum of the observational time (patient year) over all participants in this treatment group.	28 weeks
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Symptoms Score After 28 Weeks of Treatment	Positive and Negative Syndrome Scale (PANSS): assesses the severity of psychotic symptoms and progression of disease.; The PANSS positive symptoms score is the sum of scores from 7 Items where each item has a minimum score 1 (better outcome) and maximum score 7 (worse outcome). The PANSS positive symptoms score ranges from 7 (less severe the disease) to 49 (more severe the disease).	At baseline and at Week 28.
Secondary	Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Scale Score After 28 Weeks of Treatment	Clinical Global Impressions-Severity (CGI-S): One-item evaluation completed by the clinician to measure the severity of psychopathology.; The CGI-S score ranges from 1 (normal) through to 7 (most severely ill). The higher the score, the worse the psychopathology.	At baseline and at Week 28
Secondary	Patient Global Impressions-Improvement (PGI-I) Scale Score After 28 Weeks of Treatment	Patient Global Impressions-Improvement (PGI-I): One-item evaluation completed by the patient to assess their overall evaluation of his/her status compared to how they felt at randomisation.; The PGI-I score ranges from 1 (Very much better) through to 7 (Very much worse). The higher the score, the worse the improvement.	At Week 28
Secondary	Incidence Rate of Suicidal Ideation and Behaviour (Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)) After 28 Weeks of Treatment	Columbia Suicide Severity Rating Scale (C-SSRS): suicide risk assessment. At a minimum, the interview consists of 2 screening questions related to suicidal ideation and 4 related to suicidal behavior, and may be expanded to up to 17 items in case of positive responses. Free text entries are allowed.; Suicidal behavior is collected in nominal scale as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior.; Suicidal ideation is rated on a 6-point scale from 0 (No ideation present) to 5 (Active ideation with plan and intent). A score of 4 or 5 on this scale indicates serious suicidal ideation.; For each treatment group, the incidence rate was calculated as the number of events / sum of the observational time (patient year) over all participants in this treatment group.	28 weeks
Secondary	Change From Baseline in Personal and Social Performance Scale (PSP) Score After 28 Weeks of Treatment	Personal and Social Performance scale (PSP): The PSP is a 100-point, single item, clinician rated scale to assess 4 domains of social functioning (Four domains over the past month: (1) socially useful activities, (2) personal and social relationships, (3) self-care and (4) disturbing and aggressive behaviors.) in patients with schizophrenia. The PSP score is a single score ranging from 1 to 100. Higher scores represent better personal and social functioning.	At baseline and at Week 28
Secondary	Incidence Rate of New Prescription or Increase in Dose of an Ongoing Antipsychotic Medication	The incidence rate of new prescription or increase in dose of an ongoing antipsychotic medication is reported. For each treatment group, the incidence rate was calculated as the number of events / sum of the observational time (patient year) over all participants in this treatment group.	28 weeks

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