Phase 2 N=215 Randomized Double-blind Treatment

Adjuvant Treatment With a Glycine Uptake Inhibitor in Participants With Negative Symptoms of Schizophrenia (P05695) (MK-8435-001)

Schizophrenia

Bottom Line

View on ClinicalTrials.gov: NCT00725075 ↗

Enrolled (actual)

215

Serious AEs

2.3%

Results posted

Dec 2016

Primary outcome: Primary: Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12 — -13.50; -10.91; -11.21 Score on a Scale — p=0.267

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: MK-8435 (Org 25935) 4-8 mg (Drug); Placebo (Drug); MK-8435 (Org 25935) 12-16 mg (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Merck Sharp & Dohme LLC
Primary completion: Oct 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12	-13.50; -10.91; -11.21	0.267
SECONDARY Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12	-11.84; -10.69; -9.73	—
SECONDARY Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12	-0.95; -0.76; -0.56	—
SECONDARY Change From Baseline in Perception of Emotions Score at Week 12	1.42; 1.55; -0.80	—
SECONDARY Change From Baseline in Non-Verbal Reasoning Score at Week 12	0.65; 0.66; 0.78	—
SECONDARY Change From Baseline in Verbal Memory Score at Week 12	-0.76; 0.41; -0.78	—
SECONDARY Change From Baseline in Visual Memory Score at Week 12	-0.35; -1.73; -1.34	—
SECONDARY Change From Baseline in Speed of Complex Information Processing Score at Week 12	5.62; 5.73; 5.17	—
SECONDARY Change From Baseline in Working Memory Score at Week 12	0.96; 0.37; 0.82	—
SECONDARY Change From Baseline in Sustained Attention Score at Week 12	0.96; 3.81; 1.95	—
SECONDARY Change From Baseline in Executive Functioning Score at Week 12	10.16; 9.33; 12.57	—
SECONDARY Change From Baseline in Composite Memory Score at Week 12	-1.26; -1.32; -2.12	—
SECONDARY Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12	-0.8; -0.3; -1.0	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00725075). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.