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

NCT ID: NCT03055338

Last Updated: 2024-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-08
• Study Completion Date: 2018-01-09

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.

Conditions

Schizophrenia, Acute Episode

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

MK-8189

Intervention Type: DRUG

Oral CR tablets (4 mg) administered QD at the following dose strengths: 4 mg (1 tablet); 8 mg (2 tablets); 12 mg (3 tablets)

Placebo matching risperidone

Intervention Type: DRUG

Oral placebo capsule(s) matching the risperidone capsule, administered QD.

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.

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Oral capsules (2 mg) administered QD at the following dose strengths: 2 mg (1 capsule); 4 mg (2 capsules); 6 mg (3 capsules)

Placebo matching MK-8189

Intervention Type: DRUG

Oral placebo tablet(s) matching the MK-8189 tablet, administered QD.

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.

Group Type: PLACEBO_COMPARATOR

Placebo matching MK-8189

Intervention Type: DRUG

Oral placebo tablet(s) matching the MK-8189 tablet, administered QD.

Placebo matching risperidone

Intervention Type: DRUG

Oral placebo capsule(s) matching the risperidone capsule, administered QD.

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Placebo matching MK-8189

Oral placebo tablet(s) matching the MK-8189 tablet, administered QD.

Intervention Type: DRUG

Placebo matching risperidone

Oral placebo capsule(s) matching the risperidone capsule, administered QD.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Woodland International Research Group, LLC ( Site 0001)

Little Rock, Arkansas, United States

Woodland Research Northwest, LLC ( Site 0014)

Rogers, Arkansas, United States

CITRIALS ( Site 0013)

Bellflower, California, United States

Comprehensive Clinical Development ( Site 0049)

Cerritos, California, United States

Collaborative Neuroscience Network, LLC ( Site 0057)

Garden Grove, California, United States

Behavioral Research Specialists, LLC ( Site 0006)

Glendale, California, United States

Synergy East ( Site 0003)

Lemon Grove, California, United States

NRC Research Institute ( Site 0043)

Orange, California, United States

CNRI - Los Angeles, LLC ( Site 0026)

Pico Rivera, California, 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, United States

Larkin Community Hospital Behavioral Health Services ( Site 0020)

Hollywood, Florida, United States

Clinical Research Centers of America, LLC ( Site 0038)

Oakland Park, Florida, United States

Aspire Health Partners ( Site 0016)

Orlando, Florida, United States

Radiant Research - Atlanta ( Site 0008)

Atlanta, Georgia, United States

Atlanta Center For Medical Research ( Site 0056)

Atlanta, Georgia, United States

Alexian Center for Psychiatric Research ( Site 0015)

Hoffman Estates, Illinois, United States

Lake Charles Clinical Trials, LLC ( Site 0040)

Lake Charles, Louisiana, United States

CBH Health, LLC ( Site 0022)

Gaithersburg, Maryland, United States

Precise Research Centers ( Site 0018)

Flowood, Mississippi, United States

Psych Care Consultants Research ( Site 0025)

St Louis, Missouri, United States

St. Louis Clinical Trials, LLC ( Site 0012)

St Louis, Missouri, United States

Altea Research Institute ( Site 0017)

Las Vegas, Nevada, United States

Radiant Research -CliniLabs ( Site 0037)

New York, New York, United States

Midwest Clinical Research Unit ( Site 0041)

Dayton, Ohio, United States

InSite Clinical Research ( Site 0033)

DeSoto, Texas, United States

Pillar Clinical Research, LLC ( Site 0004)

Richardson, Texas, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 38851166 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-8189-005

Identifier Type: OTHER

Identifier Source: secondary_id

8189-005

Identifier Type: -

Identifier Source: org_study_id