Clinical trial NCT03230097: This Study Tests Whether BI 409306 Prevents Patients With a Specific Type of Mental Illness (Attenuated Psychosis Syndrome) From Becoming Worse. This Study Looks at How Well Patients Tolerate the Medicine and How Effective it is Over 1 Year
Official title: A Phase II Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered BI 409306 During a 52-week Treatment Period as an Early Intervention in Patients With Attenuated Psychosis Syndrome.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Psychotic Disorders
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-07-26
Enrollment: 50
Sex: ALL
Minimum age (years): 16
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a study in people between 16 and 30 years of age who have a specific type of mental illness called attenuated psychosis syndrome (APS). The purpose of this study is to find out whether BI 409306 helps reduce the symptoms of APS.

Participants are in the study for 1 year and 2 months. During this time, they visit the study site about 15 times and get about 10 phone calls. Participants are put into 2 groups by chance. They get either BI 409306 or placebo. Placebo tablets look like BI 409306 tablets but do not contain any medicine. Participants take a BI 409306 or placebo tablet two times a day.

During the study, participants answer questions in interviews and complete questionnaires so the doctors can check whether the APS symptoms change. The doctors also check the general health of the participants.


Eligibility criteria: Inclusion criteria

* Meet diagnostic criteria for attenuated psychosis syndrome as defined in DSM-5 and determined by SIPS administered at screening and diagnosis confirmed by NeuroCog Trials after review of video-taped SIPS interview.
* Age ≥16 and ≤ 30 years at the time of consent/assent.
* Male or female patients willing to use highly effective methods of contraception.

  * Female patients of childbearing potential must be ready and able to use highly effective methods of birth control per 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 Good Clinical Practice (GCP) and local legislation prior to any study-related procedures OR signed and dated informed consent provided by the patient's parent(s) (or legal guardian) and assent by the patient prior to any study-related procedures in accordance with GCP and local legislation. If the patient has a legal representative, then this legal representative must give written informed consent as well.

Exclusion criteria

* Present or past diagnosis of schizophrenia, schizophreniform, schizoaffective disorder, bipolar disorder I, major depressive disorder with psychotic features, delusional disorder, brief psychotic disorder, other specified schizophrenia spectrum and other psychotic disorder (except attenuated psychosis syndrome), and unspecified schizophrenia spectrum and other psychotic disorder, according to DSM-5.
* Patients taking antipsychotic medication for less than 8 weeks, or patients taking antipsychotic medication for a longer duration but who have not been on a stable dose for 8 weeks prior to informed consent.
* Patients who begin taking an antipsychotic between Visit 1 and Visit 2.
* Patients who have discontinued an antipsychotic medication less than two weeks prior to randomization.
* Patients taking Clozapine.
* Suicidal behavior in the past 2 years reported in the Columbia Suicide Severity Rating Scale (C-SSRS) with a lethality of attempt ≥1, or with a lethality of 0 but a potential lethality of 2, or that in the judgement of the investigator would jeopardize the patient's safety while participating in the trial. The investigator/qualified rater must review all screening C-SSRS reports prior to randomization, documenting an additional interview assessing lethality of the behavior history when appropriate.
* 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.
* Known diseases of the central nervous system (including but not limited to any kind of seizures or stroke).
* History of significant head injury (\>5 minutes without consciousness).
* A serious developmental disorder that in the judgement of the investigator would inhibit the patient's ability to comply with all study procedures, or mental retardation (documented IQ \<70), or acute attenuated symptoms exclusively related to intoxication from a psychotropic substance.
* 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.
* Meets criteria for Substance Use Disorder (DSM-5) within the six months prior to informed consent/assent.
* 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 a strong or moderate inhibitor 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 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 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
* Previous participation in any BI 409306 study.
* Further exclusion criteria apply

Primary outcomes:
measure: Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe
timeFrame: Up to 52 weeks.
Secondary outcomes:
measure: Incidence of First Episode of Psychosis
timeFrame: Up to 52 weeks.
measure: Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment
timeFrame: Baseline, week 24 and week 52.
measure: Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment
timeFrame: Baseline and week 52.
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment
timeFrame: Baseline and week 52.
Other outcomes:
Locations:
city: Culver City
country: United States
facility: ProScience Research Group
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: New Haven
country: United States
facility: PRIME Clinic
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Clinical Research Institute PC
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Cherry Health
state: Michigan
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Cherry Hill
country: United States
facility: Center For Emotional Fitness
state: New Jersey
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Eugene
country: United States
facility: PeaceHealth Medical Group
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: Irving
country: United States
facility: University Hills Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Psychiatric and Behavioral Solutions, LLC
state: Utah
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital (University of Alberta)
state: Alberta
city: Chatham
country: Canada
facility: Chatham-Kent Clinical Trials Research Centre
state: Ontario
city: Toronto
country: Canada
facility: Alan D. Lowe Medicine Professional Corporation
state: Ontario
city: Beijing
country: China
facility: Peking University Sixth Hospital
city: Shanghai
country: China
facility: Shanghai Mental Health Center
city: Antrim
country: United Kingdom
facility: Holywell Hospital
city: Birmingham
country: United Kingdom
facility: The Barberry National Centre for Mental Health
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: University of Manchester
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Keefe RSE, Woods SW, Cannon TD, Ruhrmann S, Mathalon DH, McGuire P, Rosenbrock H, Daniels K, Cotton D, Roy D, Pollentier S, Sand M. A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale. Early Interv Psychiatry. 2021 Oct;15(5):1315-1325. doi: 10.1111/eip.13083. Epub 2020 Dec 22.