An Active-Controlled Early Phase Study of MK-8189 in Adults With Schizophrenia (MK-8189-005)

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia, Acute Episode
• Intervention / Treatment: Drug: MK-8189; Drug: Placebo matching risperidone; Drug: Risperidone; Drug: Placebo matching MK-8189

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, LLC ( Site 0001)
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest, LLC ( Site 0014)
  • California
    • Bellflower, California, United States, 90706
      • CITRIALS ( Site 0013)
    • Cerritos, California, United States, 90703
      • Comprehensive Clinical Development ( Site 0049)
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC ( Site 0057)
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC ( Site 0006)
    • Lemon Grove, California, United States, 91945
      • Synergy East ( Site 0003)
    • Orange, California, United States, 92868
      • NRC Research Institute ( Site 0043)
    • Pico Rivera, California, United States, 90660
      • CNRI - Los Angeles, LLC ( Site 0026)
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research ( Site 0027)
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute ( Site 0032)
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Network, LLC ( Site 0046)
  • Florida
    • Hollywood, Florida, United States, 33021
      • Larkin Community Hospital Behavioral Health Services ( Site 0020)
    • Oakland Park, Florida, United States, 33334
      • Clinical Research Centers of America, LLC ( Site 0038)
    • Orlando, Florida, United States, 32810
      • Aspire Health Partners ( Site 0016)
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Radiant Research - Atlanta ( Site 0008)
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center For Medical Research ( Site 0056)
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Center for Psychiatric Research ( Site 0015)
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials, LLC ( Site 0040)
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health, LLC ( Site 0022)
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers ( Site 0018)
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Psych Care Consultants Research ( Site 0025)
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials, LLC ( Site 0012)
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research Institute ( Site 0017)
  • New York
    • New York, New York, United States, 10019
      • Radiant Research -CliniLabs ( Site 0037)
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Unit ( Site 0041)
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research ( Site 0033)
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research, LLC ( Site 0004)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-8189; Participants receive MK-8189 (4 mg controlled release [CR] oral tablet[s]) in combination with placebo matching risperidone (oral capsule[s]) once daily (QD) for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is also titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.	Drug: MK-8189; Oral CR tablets (4 mg) administered QD at the following dose strengths: 4 mg (1 tablet); 8 mg (2 tablets); 12 mg (3 tablets); Drug: Placebo matching risperidone; Oral placebo capsule(s) matching the risperidone capsule, administered QD.
Active Comparator: Risperidone; Participants receive risperidone (2 mg oral capsule[s]) in combination with placebo matching MK-8189 (oral tablet[s]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is also titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Drug: Risperidone; Oral capsules (2 mg) administered QD at the following dose strengths: 2 mg (1 capsule); 4 mg (2 capsules); 6 mg (3 capsules); Drug: Placebo matching MK-8189; Oral placebo tablet(s) matching the MK-8189 tablet, administered QD.
Placebo Comparator: Placebo; Participants receive both placebo matching MK-8189 (oral tablet[s]) as well as placebo matching Risperidone (oral capsule[s]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.	Drug: Placebo matching risperidone; Oral placebo capsule(s) matching the risperidone capsule, administered QD.; Drug: Placebo matching MK-8189; Oral placebo tablet(s) matching the MK-8189 tablet, administered QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): January 9, 2018
• Study Completion (Actual): January 9, 2018

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 16, 2017

Study Record Updates

• Last Update Posted (Actual): December 26, 2018
• Last Update Submitted That Met QC Criteria: December 6, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia, acute episode
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 8189-005; MK-8189-005 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No