Clinical trial NCT03055338: An Active-Controlled Early Phase Study of MK-8189 in Adults With Schizophrenia (MK-8189-005)
Official title: A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Efficacy and Safety of MK-8189 Using Risperidone as an Active Control in Subjects Experiencing an Acute Episode of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia, Acute Episode
Keywords: Schizophrenia, acute episode
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-02-16
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to one of three groups in parallel for the duration of the study.
Primary purpose: TREATMENT

Brief summary: This will be a randomized, placebo-controlled, parallel-group, multi-site, double-blind trial of MK-8189 compared with placebo, using Risperidone as an active control. The participants will be adult subjects experiencing an acute episode of schizophrenia, according to the criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5). This study will be up to 7 weeks in duration, with up to 7 site visits for each participant. The study will consist of a Screening/tapering period (up to one week long), a 4-week treatment period, and a 14-day follow-up period. The primary objective will be to assess symptoms of schizophrenia at 4 weeks, and to assess safety and tolerability during treatment and post-treatment follow-up. The secondary objective will be to assess the severity of schizophrenia at 4 weeks. The primary hypothesis is that MK-8189 is superior to placebo in reducing the overall symptoms of schizophrenia as assessed by the mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score after 4 weeks of treatment.


Eligibility criteria: Inclusion Criteria:

* 18 to 50 years of age at Screening
* Male
* Female not of reproductive potential (e.g., postmenopausal or has had a hysterectomy), or agrees to practice abstinence or use acceptable contraception
* Meets the diagnostic criteria for schizophrenia according to the DSM-5 criteria, or has a past diagnosis of schizophrenia with the onset of the first episode being \>=1 year prior to study entry, and has illness duration of \<=20 years
* Is confirmed to be experiencing an acute episode of schizophrenia
* Minimum PANSS score \>= 80 at Screening
* Has a score of \>=4 in 3 or more of the following items (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/persecution) in the positive subscale of the PANSS at Screening
* Has a CGI-S score \>= 4 at Screening
* Is able to taper off psychotropic medications without significant destabilization or increased suicidality
* Has responded positively to an antipsychotic medication other than clozapine in a prior psychotic episode
* Has an identified responsible external contact person who has regular contact (no less than once per week) with the participant

Exclusion Criteria:

* Is currently under involuntary commitment because he/she is considered a danger to himself/herself or others
* Is unwilling to remain hospitalized for the duration of trial treatment
* Is currently participating in or has participated in an interventional clinical research study \<=6 months prior to Screening, or has participated in more than one interventional clinical trial research study within 12 months prior to Screening
* Is unwilling to allow audio/video taping of the Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI) and/or PANSS interview at Screening and Baseline
* Is currently being treated with and benefiting from medications with a moderate or strong inhibiting or inducing effect on Cytochrome P450 (CYP) 3A and/or CYP2C9 and/or sensitive substrates of CYP2B6
* Has a history of malignancy \<= 5 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
* Has a body mass index \<18.5 or \>40 kg/m˄2
* Has a history of treatment-resistant schizophrenia
* Has a prolactin laboratory value of \>= 5 times the upper limit of normal at Screening
* Has a known history or clinical evidence of clinically significant hepatic, cardiovascular, or renal disease, or of untreated narrow-angle glaucoma- Has ever been diagnosed with epilepsy or had any seizure disorder beyond one childhood febrile seizure
* Has known serological evidence of human immunodeficiency virus (HIV) antibody
* Has a history of neuroleptic malignant syndrome
* Has a current diagnosis other than schizophrenia, or a comorbid diagnosis primarily responsible for current symptoms and functional impairment
* Has a known history of borderline personality disorder, antisocial personality disorder, or bipolar disorder
* Has a known history of traumatic brain injury, or Alzheimer's disease or another form of dementia
* Currently meets DSM-5 criteria for substance abuse or alcohol use disorder
* Is at imminent risk of self-harm or harm to others

Primary outcomes:
measure: Least Squares Mean (LSM) Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
timeFrame: Baseline and Week 4
measure: Percentage of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 6 weeks
measure: Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Least Squares Mean (LSM) Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 4
timeFrame: Baseline and Week 4
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC ( Site 0001)
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest, LLC ( Site 0014)
state: Arkansas
city: Bellflower
country: United States
facility: CITRIALS ( Site 0013)
state: California
city: Cerritos
country: United States
facility: Comprehensive Clinical Development ( Site 0049)
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC ( Site 0057)
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC ( Site 0006)
state: California
city: Lemon Grove
country: United States
facility: Synergy East ( Site 0003)
state: California
city: Orange
country: United States
facility: NRC Research Institute ( Site 0043)
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles, LLC ( Site 0026)
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research ( Site 0027)
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute ( Site 0032)
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC ( Site 0046)
state: California
city: Hollywood
country: United States
facility: Larkin Community Hospital Behavioral Health Services ( Site 0020)
state: Florida
city: Oakland Park
country: United States
facility: Clinical Research Centers of America, LLC ( Site 0038)
state: Florida
city: Orlando
country: United States
facility: Aspire Health Partners ( Site 0016)
state: Florida
city: Atlanta
country: United States
facility: Radiant Research - Atlanta ( Site 0008)
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center For Medical Research ( Site 0056)
state: Georgia
city: Hoffman Estates
country: United States
facility: Alexian Center for Psychiatric Research ( Site 0015)
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials, LLC ( Site 0040)
state: Louisiana
city: Gaithersburg
country: United States
facility: CBH Health, LLC ( Site 0022)
state: Maryland
city: Flowood
country: United States
facility: Precise Research Centers ( Site 0018)
state: Mississippi
city: Saint Louis
country: United States
facility: Psych Care Consultants Research ( Site 0025)
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials, LLC ( Site 0012)
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute ( Site 0017)
state: Nevada
city: New York
country: United States
facility: Radiant Research -CliniLabs ( Site 0037)
state: New York
city: Dayton
country: United States
facility: Midwest Clinical Research Unit ( Site 0041)
state: Ohio
city: DeSoto
country: United States
facility: InSite Clinical Research ( Site 0033)
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC ( Site 0004)
state: Texas
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Mukai Y, Lupinacci R, Marder S, Snow-Adami L, Voss T, Smith SM, Egan MF. Effects of PDE10A inhibitor MK-8189 in people with an acute episode of schizophrenia: A randomized proof-of-concept clinical trial. Schizophr Res. 2024 Aug;270:37-43. doi: 10.1016/j.schres.2024.05.019. Epub 2024 Jun 8.