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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Schizophrenia, Acute Episode

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03055338

8189-005

MK-8189-005 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 224 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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224 participants in 3 patient groups, including a placebo group

MK-8189

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching risperidone

Drug: MK-8189

Risperidone

Active Comparator group

Description:

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.

Treatment:

Drug: Risperidone

Drug: Placebo matching MK-8189

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo matching risperidone

Drug: Placebo matching MK-8189