Schizophrenia, Acute Episode Clinical Trial
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
| Verified date | November 2018 |
| Source | Merck Sharp & Dohme Corp. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 224 |
| Est. completion date | January 9, 2018 |
| Est. primary completion date | January 9, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 50 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Atlanta Center For Medical Research ( Site 0056) | Atlanta | Georgia |
| United States | Radiant Research - Atlanta ( Site 0008) | Atlanta | Georgia |
| United States | CITRIALS ( Site 0013) | Bellflower | California |
| United States | Comprehensive Clinical Development ( Site 0049) | Cerritos | California |
| United States | Midwest Clinical Research Unit ( Site 0041) | Dayton | Ohio |
| United States | InSite Clinical Research ( Site 0033) | DeSoto | Texas |
| United States | Precise Research Centers ( Site 0018) | Flowood | Mississippi |
| United States | CBH Health, LLC ( Site 0022) | Gaithersburg | Maryland |
| United States | Collaborative Neuroscience Network, LLC ( Site 0057) | Garden Grove | California |
| United States | Behavioral Research Specialists, LLC ( Site 0006) | Glendale | California |
| United States | Alexian Center for Psychiatric Research ( Site 0015) | Hoffman Estates | Illinois |
| United States | Larkin Community Hospital Behavioral Health Services ( Site 0020) | Hollywood | Florida |
| United States | Lake Charles Clinical Trials, LLC ( Site 0040) | Lake Charles | Louisiana |
| United States | Altea Research Institute ( Site 0017) | Las Vegas | Nevada |
| United States | Synergy East ( Site 0003) | Lemon Grove | California |
| United States | Woodland International Research Group, LLC ( Site 0001) | Little Rock | Arkansas |
| United States | Radiant Research -CliniLabs ( Site 0037) | New York | New York |
| United States | Clinical Research Centers of America, LLC ( Site 0038) | Oakland Park | Florida |
| United States | NRC Research Institute ( Site 0043) | Orange | California |
| United States | Aspire Health Partners ( Site 0016) | Orlando | Florida |
| United States | CNRI - Los Angeles, LLC ( Site 0026) | Pico Rivera | California |
| United States | Pillar Clinical Research, LLC ( Site 0004) | Richardson | Texas |
| United States | Woodland Research Northwest, LLC ( Site 0014) | Rogers | Arkansas |
| United States | Psych Care Consultants Research ( Site 0025) | Saint Louis | Missouri |
| United States | St. Louis Clinical Trials, LLC ( Site 0012) | Saint Louis | Missouri |
| United States | Artemis Institute for Clinical Research ( Site 0027) | San Diego | California |
| United States | Schuster Medical Research Institute ( Site 0032) | Sherman Oaks | California |
| United States | Collaborative Neuroscience Network, LLC ( Site 0046) | Torrance | California |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme Corp. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Least Squares Mean (LSM) Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | The LSM change from baseline at week 4 was assessed for PANSS total score. The PANSS assesses the severity of schizophrenia symptoms through a clinician-rated inventory of 30 items organized in 3 subscales: 1) positive subscale (7 items); 2) negative subscale (7 items); and 3) general psychopathology subscale (16 items). For each item, symptoms are scored from 1 (absent) to 7 (extreme) and sum to a total PANSS score (range: 30-210). Higher scores reflect more severe symptoms of schizophrenia. Further, reduced symptom severity over time is reflected by decreases in score. | Baseline and Week 4 | |
| Primary | Percentage of Participants Experiencing an Adverse Event (AE) | The percentage of participants experiencing an AE was assessed. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Up to 6 weeks | |
| Primary | Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event | The percentage of participants discontinuing study treatment due to an AE was assessed. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Up to 4 weeks | |
| Secondary | Least Squares Mean (LSM) Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 4 | The LSM change from baseline at week 4 was assessed for CGI-S score. The CGI-S is a 7-point clinician-rated scale for assessing the global severity of the participant's illness. Possible CGI-S scores range from 1 (participant normal, not ill) to 7 (participant extremely ill). Further, a decrease in CGI-S score indicates reduced severity of the participant's illness. | Baseline and Week 4 |