Translational Neuroscience Optimization of GlyT1 Inhibitor

NCT01911676 | Completed Phase 2 Results DMC

• 2 other identifiers: 13030117164UH3TR000960-02
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase II, randomized, double-blind, placebo-controlled, cross-over POC study of stable patients with Schizophrenia or Schizoaffective disorder. The primary objective of this study is to test the efficacy of treatment with one of two does of a glycine transporter inhibitor (GlyT1I) combined with cognitive remediation to enhavce cognitive function. Subjects will be randomized to one of two doses of the glycine transporter inhibitor (GlyT1I) and placebo twice daily in addition to their antipsychotic medication for 2 treatment periods, each lasting a minimum of 5 weeks. Treatment periods will be separated by a washout period lasting approximately 3 weeks.

Conditions

Cognitive Impairments Associated With Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)

  To test the efficacy of PF-03463275 on cognitive test performance specifically, the MCCB composite score was used. The MCCB consists of 10 tests and provides standard scores and percentiles for each of seven cognitive domains and an overall composite score. Domains assessed include: speed of processing, attention/vigilance, working memory (verbal and visual), verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB overall composite score is presented as a T-score. The range of T-scores is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning.

  Change from baseline in cognitive measures at approximately 5 weeks. Mean scores were calculated per time point for each arm.

Secondary Outcomes (1)

• Alteration in Symptom Domain Scores and Event Related Potentials (ERPs) With PF-03463275

  Change from Baseline at approximately 1 week

Study Arms (3)

PF-03463275 Active Dose #1

EXPERIMENTAL

Active dose between 40mg

Drug: PF-03463275

PF-03463275 Active Dose #2

EXPERIMENTAL

Active dose between 60mg

Drug: PF-03463275

Placebo

PLACEBO COMPARATOR

Placebo- no active dose of PF-03463275.

Drug: Placebo

Interventions

PF-03463275 DRUG

PF-03463275 Active Dose #1; PF-03463275 Active Dose #2

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Males or females 21 to 65 years of age (inclusive).
• \) Diagnosis of Schizophrenia or Schizoaffective Disorder
• \) Able to provide written informed consent.
• \) Only CYP2D6 extensive metabolizers.

You may not qualify if:

• \) No ongoing acute medical issues
• \) Clinically significant ECG abnormality
• \) Blood donation within eight weeks of the start of the study
• \) Current treatment with Clozapine

Sponsors & Collaborators

• Yale University: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (2)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

Related Publications (1)

• Surti TS, Ranganathan M, Johannesen JK, Gueorguieva R, Deaso E, Kenney JG, Krystal JH, D'Souza DC. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophr Res. 2023 Jun;256:36-43. doi: 10.1016/j.schres.2023.04.010. Epub 2023 May 2.

  PMID: 37141764 DERIVED

MeSH Terms

Interventions

1-methyl-1H-imidazole-4-carboxylic acid (3-chloro-4-fluoro-benzyl)-(3-methyl-3-aza-bicyclo(3.1.0) hex-6-ylmethyl)amide

Results Point of Contact

• Title: Christina Luddy
• Organization: Yale University

christina.luddy@yale.edu

203-932-5711

Study Officials

• Deepak C D'Souza, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2013
• First Posted: July 30, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 19, 2024
• Results First Posted: February 27, 2023

Record last verified: 2024-08

Locations

US (2)