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

NCT03055338 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 8189-005MK-8189-005
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 28

Brief Summary

This will be a randomized, placebo-controlled, parallel-group, multi-site, double-blind trial of elpipodect 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 elpipodect 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

Keywords

Schizophrenia, acute episode; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Least Squares Mean (LSM) Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 4

  Baseline and Week 4

Study Arms (3)

Elpipodect

EXPERIMENTAL

Participants receive elpipodect (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, elpipodect 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, elpipodect is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.

Drug: Elpipodect; Drug: Placebo matching risperidone

Risperidone

ACTIVE COMPARATOR

Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching elpipodect (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 elpipodect 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 elpipodect (3 tablets), QD for 3 weeks.

Drug: Risperidone; Drug: Placebo matching MK-8189

Placebo

PLACEBO COMPARATOR

Participants receive both placebo matching elpipodect (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 elpipodect 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 elpipodect and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.

Drug: Placebo matching MK-8189; Drug: Placebo matching risperidone

Interventions

Risperidone DRUG

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

Risperidone

Elpipodect 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)

Also known as: MK-8189

Elpipodect

Placebo matching MK-8189 DRUG

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

Placebo; Risperidone

Placebo matching risperidone DRUG

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

Elpipodect; Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (28)

Woodland International Research Group, LLC ( Site 0001)

Little Rock, Arkansas, 72211, United States

Location

Woodland Research Northwest, LLC ( Site 0014)

Rogers, Arkansas, 72758, United States

Location

CITRIALS ( Site 0013)

Bellflower, California, 90706, United States

Location

Comprehensive Clinical Development ( Site 0049)

Cerritos, California, 90703, United States

Location

Collaborative Neuroscience Network, LLC ( Site 0057)

Garden Grove, California, 92845, United States

Location

Behavioral Research Specialists, LLC ( Site 0006)

Glendale, California, 91206, United States

Location

Synergy East ( Site 0003)

Lemon Grove, California, 91945, United States

Location

NRC Research Institute ( Site 0043)

Orange, California, 92868, United States

Location

CNRI - Los Angeles, LLC ( Site 0026)

Pico Rivera, California, 90660, United States

Location

Artemis Institute for Clinical Research ( Site 0027)

San Diego, California, 92103, United States

Location

Schuster Medical Research Institute ( Site 0032)

Sherman Oaks, California, 91403, United States

Location

Collaborative Neuroscience Network, LLC ( Site 0046)

Torrance, California, 90502, United States

Location

Larkin Community Hospital Behavioral Health Services ( Site 0020)

Hollywood, Florida, 33021, United States

Location

Clinical Research Centers of America, LLC ( Site 0038)

Oakland Park, Florida, 33334, United States

Location

Aspire Health Partners ( Site 0016)

Orlando, Florida, 32810, United States

Location

Radiant Research - Atlanta ( Site 0008)

Atlanta, Georgia, 30328, United States

Location

Atlanta Center For Medical Research ( Site 0056)

Atlanta, Georgia, 30331, United States

Location

Alexian Center for Psychiatric Research ( Site 0015)

Hoffman Estates, Illinois, 60169, United States

Location

Lake Charles Clinical Trials, LLC ( Site 0040)

Lake Charles, Louisiana, 70629, United States

Location

CBH Health, LLC ( Site 0022)

Gaithersburg, Maryland, 20877, United States

Location

Precise Research Centers ( Site 0018)

Flowood, Mississippi, 39232, United States

Location

Psych Care Consultants Research ( Site 0025)

St Louis, Missouri, 63128, United States

Location

St. Louis Clinical Trials, LLC ( Site 0012)

St Louis, Missouri, 63141, United States

Location

Altea Research Institute ( Site 0017)

Las Vegas, Nevada, 89102, United States

Location

Radiant Research -CliniLabs ( Site 0037)

New York, New York, 10019, United States

Location

Midwest Clinical Research Unit ( Site 0041)

Dayton, Ohio, 45417, United States

Location

InSite Clinical Research ( Site 0033)

DeSoto, Texas, 75115, United States

Location

Pillar Clinical Research, LLC ( Site 0004)

Richardson, Texas, 75080, United States

Location

Related Publications (1)

• 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.

  PMID: 38851166 RESULT

MeSH Terms

Conditions

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Interventions

MK-8189; Risperidone

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A double-blind/masking technique will be used. MK-8189 and risperidone will be packaged identically relative to their respective matching placebo so that blinding/masking is maintained.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to one of three groups in parallel for the duration of the study.

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: February 16, 2017
• Study Start: March 8, 2017
• Primary Completion: January 9, 2018
• Study Completion: January 9, 2018
• Last Updated: April 29, 2026
• Results First Posted: December 26, 2018

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)