Add On Treatment for Cognitive Deficits in Schizophrenia

NCT01346163 | Completed Phase 1

• 1 other identifier: 809087
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study will look at the impact of dosing as well as ongoing treatment with an investigation medication identified as PF-03654746, on cognitive and physiologic indicators of brain function. Data from this study will assist with the evaluation of the utility of functional magnetic resonance imaging, arterial spin labeling (ASL), and electrophysiologic measures in the detection of early signals of the effectiveness of medications developed to target cognitive impairment in schizophrenia. Safety and tolerability of PF-03654746 in this population will be also be evaluated.

Conditions

Schizophrenia

Keywords

Schizophrenia; Cognitive Impairment; Electrophysiology; H3 receptor antagonist

Outcome Measures

Primary Outcomes (1)

• MATRICS Consensus Cognitive Battery

  13 - 15 Weeks

Secondary Outcomes (3)

• ASL perfusion and performance on neurocognitive measures

  3 Weeks

• fMRI activation parameters and performance on neurocognitive measures.

  3 weeks

• ERP measures and performance on neurocognitive measures

  3 Weeks

Study Arms (2)

PF-03654746

ACTIVE COMPARATOR

H3 receptor antagonist currently being developed for the treatment of cognitive impairment associated with schizophrenia (CIAS) as well as with Alzheimer's disease.

Drug: PF 03654746

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

PF 03654746 DRUG

All participants will receive 3 weeks of PF-03654746 and 3 weeks of placebo. PF-03654746 and placebo will be administered in a flexible titration regimen, beginning with 0.5 mg/d. If 0.5 mg/d is well tolerated, the dose will be increased to 1.0 mg/d after 5 days. If 1.0 mg/d is not well tolerated, the dose will be decreased to 0.5 mg/d, with the goal of achieving a stable dose of PF-03654746 within the first two weeks of dosing and avoiding further dose changes during the final week of dosing.

PF-03654746

Placebo OTHER

Placebo will be used as a comparator to the active arm.

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be competent to provide informed consent to participate in a clinical trial before any trial-related procedures can take place;
• Subjects must be willing and able to comply with scheduled visits, treatments, laboratory tests and other testing and study procedures;
• Subjects who participate must be willing to remain in-patient for at least one week at the beginning of each treatment period and remain in the hospital until judged by the Investigator to be clinically stable and able to be discharged to outpatient status;
• Subjects must be fluent in English and able to understand all study related materials;
• Subjects must be between the ages of 18-40 (inclusive) and if Female be of non-childbearing potential;
• Body Mass Index (BMI) 18 to 40 kg/m2 and a total body weight of at least 50 kg (110 lbs);
• Subjects must have a current DSM-IV-TR diagnosis of schizophrenia of Paranoid (295.30), Disorganized (295.10), Undifferentiated (295.90) or Residual Type (295.60);
• Subjects must be receiving ongoing maintenance antipsychotic monotherapy with risperidone, olanzapine, quetiapine, ziprasidone, paliperidone or aripiprazole;
• Subjects must be on a stable medication treatment regimen 2 months, including concomitant psychotropic medications;
• Evidence of stable control of symptoms for 3 months (eg, no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of symptoms of schizophrenia);
• No more than moderate severity rating (4) on any individual PANSS positive symptom item (P1, P3, P5, P6) or formal thought disorder (P2), with no more than two moderate items in total;
• Calgary Depression Scale Score less than or equal to 10;
• Subjects must have a minimal level of extrapyramidal symptoms as documented by a score on the ESRS-A Global Parkinsonism scale of 3;
• Subjects must have an illness duration (from the time of diagnosis) of at least 1 year;
• Subjects will meet the following cognitive performance criteria:

You may not qualify if:

• Female subjects who still have child bearing potential and females who are breastfeeding;
• History of febrile illness within 5 days prior to the first dose;
• Any condition possibly affecting drug absorption (eg, gastrectomy);
• Subjects who have a positive urine drug screen which cannot be explained by prescribed medications;
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening;
• Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication;
• lead ECG demonstrating QTc less than or equal to 450 msec at screening;
• Subjects who are using disallowed concomitant medications and who will not be able to discontinue these concomitant medications prior to randomization;
• Subjects who have taken hormone replacement therapy within 28 days or have taken an herbal remedy 7 days prior to the first dose of trial medication;
• Subjects with other conditions that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results, and in the judgment of the Investigator, would make the subject inappropriate for entry into this trial;
• Subjects with serologic evidence of acute hepatitis or chronic hepatitis and subjects with known hepatitis C antibodies and elevated LFTs;
• Subjects with AST and/or ALT 1.5xULN at the Screening Visit;
• Subjects with a current DSM-IV axis I diagnosis other than schizophrenia;
• Subjects with a concurrent psychiatric disorder other than schizophrenia coded on Axis I;
• Subjects who have previously participated in a trial using PF-03654746;

Sponsors & Collaborators

• University of Pennsylvania: lead
• Pfizer: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• University of Pennsylvania Department of Neuropsychiatry Home Page

MeSH Terms

Conditions

Schizophrenia; Cognitive Dysfunction

Interventions

N-ethyl-3-fluoro-3-(3-fluoro-4-(pyrrolidinylmethyl)phenyl)cyclobutanecarboxamide

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Officials

• Raquel P. Gur, M.D., Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 20, 2009
• First Posted: May 2, 2011
• Study Start: April 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: May 2, 2011

Record last verified: 2011-04

Locations

US (1)