Adjuvant Treatment With a Glycine Uptake Inhibitor in Participants With Negative Symptoms of Schizophrenia (P05695) (MK-8435-001)
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: MK-8435 (Org 25935) 4-8 mg; Placebo; MK-8435 (Org 25935) 12-16 mg
Intervention description: Administered orally 2 times a day (BID) for a final concentration of 8-16 mg/day; Matching placebo for MK-8435 (Org 25935) administered orally BID; Administered orally BID for a final concentration of 24-32 mg/day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Negative symptoms; Glycine Uptake inhibitor; Add-on treatment; Second Generation Antipsychotic

Summary:

      The purpose of this study is to determine whether MK-8435 (Org 25935) is more effective than
      placebo in improving negative symptoms in participants with schizophrenia who are
      concurrently treated with a stable dose of a second generation antipsychotic.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is diagnosed with non-first episode schizophrenia meeting Diagnostic and Statistical
             Manual (Version IV) criteria

          -  Is receiving stable treatment with one of the following SGA: aripiprazole, olanzapine,
             quetiapine, risperidone, or ziprasidone

          -  Is in the non-acute phase of illness and clinically stable for 3 months prior to study
             start as demonstrated by: treatment with current SGA or at least 12 weeks prior to
             study start; no increase in the level of psychiatric care due to worsening symptoms
             for at least 12 weeks prior to study start; and no dose change of SGA or change in
             medication to treat the symptoms of schizophrenia for 4 weeks prior to study start

          -  Has a score ≥4 on 3 or more of the following Positive and Negative Symptoms Scale
             (PANSS) negative subscale items at study start: blunted affect, emotional withdrawal,
             poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and
             active social avoidance

          -  Has an overall PANSS negative subscale score > 20

        Exclusion Criteria:

          -  Has an overall PANSS positive subscale score ≥20

          -  Has a score ≥5 on 2 or more of the following PANSS positive subscale items at study
             start: delusions, hallucinatory behavior, excitement, grandiosity, or
             suspiciousness/persecution

          -  Has a score ≥9 on the modified InterSePT Scale for Suicidal Thinking

          -  Has a score ≥9 on the Calgary Depression Scale for Schizophrenia

          -  Has a score ≥3 on the clinical global impression of Parkinsonism of the abbreviated
             Extrapyramidal Symptom Rating Scale

          -  Has untreated or uncompensated clinically significant renal, endocrine, hepatic,
             respiratory, cardiovascular, hematological, immunological or cerebrovascular disease,
             malignancy, or other chronic and/or degenerative process

          -  Has a history of seizure disorder beyond childhood or is taking any anticonvulsants to
             prevent seizures

          -  Has a diagnosis of mental retardation or organic brain syndrome

          -  Has a clinically relevant visual disturbance, such as cataract, color blindness,
             macular degeneration, glaucoma, or retinal disease

          -  Has a concurrent diagnosis of substance dependence other than nicotine or caffeine
             dependence in the past 6 months prior to study start

          -  Has a positive result on the urine alcohol/drug screen for alcohol or illicit drugs

          -  Is pregnant or breastfeeding

          -  Is being treated with high doses of benzodiazepines (>4 mg per day lorazepam or
             equivalent)

          -  Has an imminent risk of self-harm or harm to others

          -  Has been treated with clozapine in the past 6 months prior to study start

          -  Has been treated with lithium, valproate, lamotrigine, pregabalin, gabapentin, or
             carbamazepine in the past 12 weeks prior to study start

          -  Has started treatment or has had a dose change of an (additional) antipsychotic,
             antidepressant,hypnotic or anxiolytic in the past 4 weeks prior to study start

          -  Has had no demonstrated benefit of antipsychotic treatment within the previous five
             years