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

NCT00725075 | Completed Phase 2 Results

• 4 other identifiers: P05695MK-8435-0011720032006-003080-31
• Study Type: interventional
• Target: 215
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Schizophrenia

Keywords

Negative symptoms; Glycine Uptake inhibitor; Add-on treatment; Second Generation Antipsychotic

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12

  SANS was a 25-item clinician-rated instrument for assessing the negative symptoms of schizophrenia. SANS 1-22 Composite Score consisted of the SANS 25 scale minus the last 3 questions (attention items). The remaining non-attention items (affective flattening, alogia, avolition-apathy, and anhedonia-asociality) comprised the SANS 1-22 Composite Score. For each item, symptom severity was rated on a 6-point scale, from 0=absent to 5=severe. The SANS 1-22 Composite Score had a total scoring range of 0 to 110. Higher scores indicated more impairment. The SANS 1-22 Composite Score was reported using data from the adjusted site rater. A negative change from baseline indicated an improvement in symptoms.

  Baseline and Week 12

Secondary Outcomes (12)

• Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12

  Baseline and Week 12

• Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12

  Baseline and Week 12

• Change From Baseline in Perception of Emotions Score at Week 12

  Baseline and Week 12

• Change From Baseline in Non-Verbal Reasoning Score at Week 12

  Baseline and Week 12

• Change From Baseline in Verbal Memory Score at Week 12

  Baseline and Week 12

Study Arms (3)

MK-8435 (Org 25935) 8-16 mg per day

EXPERIMENTAL

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.

Drug: MK-8435 (Org 25935) 4-8 mg

MK-8435 (Org 25935) 24-32 mg per day

EXPERIMENTAL

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.

Drug: MK-8435 (Org 25935) 12-16 mg

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

MK-8435 (Org 25935) 4-8 mg DRUG

Administered orally 2 times a day (BID) for a final concentration of 8-16 mg/day

MK-8435 (Org 25935) 8-16 mg per day

Placebo DRUG

Matching placebo for MK-8435 (Org 25935) administered orally BID

Placebo

MK-8435 (Org 25935) 12-16 mg DRUG

Administered orally BID for a final concentration of 24-32 mg/day

MK-8435 (Org 25935) 24-32 mg per day

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Schoemaker JH, Jansen WT, Schipper J, Szegedi A. The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial. J Clin Psychopharmacol. 2014 Apr;34(2):190-8. doi: 10.1097/JCP.0000000000000073.

  PMID: 24525661 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)aminomethylcarboxylic acid

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: July 30, 2008
• Study Start: April 10, 2007
• Primary Completion: October 24, 2008
• Study Completion: October 24, 2008
• Last Updated: October 16, 2018
• Results First Posted: December 13, 2016

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share