Conditions: Schizophrenia
Keywords: Negative symptoms Glycine Uptake inhibitor Add-on treatment Second Generation Antipsychotic
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 215
Healthy volunteers: no

Brief 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.

Detailed description:
The primary features of schizophrenia are characterized by positive (irrational thoughts and/or behavior) and negative symptoms. Negative symptoms are the gross absence of normal behavior and emotions, and usually include a general lack of engagement, social withdrawal, and loss of goal-directed behavior.

Negative symptoms may strongly affect daytime activities and quality of life. The effects of currently available antipsychotics on negative symptoms are not satisfactory and leave much room for improvement. MK-8435 (Org 25935) is an investigational drug that may help to correct the above characteristics of schizophrenia by facilitating the messenger function of an amino acid in the brain, called glutamate. Preliminary data suggest that lowered glutamate levels in schizophrenia are associated with a failure to activate relevant areas in the forebrain and with prominent negative symptoms.

Arms:
arm 1: Participants will be maintained on a stable dose of Second Generation Antipsychotic (SGA) and receive 4-8 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) can be titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose must remain stable after Day 42 for the remainder of the study. arm 2: Participants will be maintained on a stable dose of SGA and receive 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) can be titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose must remain stable after Day 42 for the remainder of the study. arm 3: Participants will be maintained on a stable dose of SGA and receive matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.

Interventions: intervention 1: MK-8435 (Org 25935) 4-8 mg intervention 2: Placebo intervention 3: MK-8435 (Org 25935) 12-16 mg
Intervention descriptions: intervention 1: Administered orally 2 times a day (BID) for a final concentration of 8-16 mg/day intervention 2: Matching placebo for MK-8435 (Org 25935) administered orally BID intervention 3: Administered orally BID for a final concentration of 24-32 mg/day

Protocol document: