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| ID | Type | Description | Link |
|---|---|---|---|
| 4UH3TR000960-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Center for Advancing Translational Sciences (NCATS) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-03463275 Active Dose #1 | Experimental | Active dose between 40mg |
|
| PF-03463275 Active Dose #2 | Experimental | Active dose between 60mg |
|
| Placebo | Placebo Comparator | Placebo- no active dose of PF-03463275. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-03463275 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Alteration in Symptom Domain Scores and Event Related Potentials (ERPs) With PF-03463275 | To determine whether PF-03463275 impacts symptom domain scores and visual event related potentials (ERPs), analogous to long-term potentiation (LTP) with PF-03463275 treatment. A more positive value reflects a better outcome - there is no established range to report. A Z-score of 0 indicates the mean score. A positive z-score indicates the mean is higher than average. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Deepak C D'Souza, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Connecticut Mental Health Center | New Haven | Connecticut | 06519 | United States | ||
| VA Connecticut Healthcare System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37141764 | Derived | 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. |
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Subjects will be randomized to one of two doses of PF-03463275 and placebo twice daily for 2 treatment periods each lasting approx 5 weeks. Treatment periods will be separated by a washout period lasting approx 3 weeks. The 4 possible study arms are as follows: A) Pd 1: Active dose 60mg PF-03463275 then Pd 2: Placebo B) Pd 1: Active dose 40mg PF-03463275 then Pd 2: Placebo C) Pd 1: Placebo then Pd 2: Active dose 60mg PF-03463275 D) Pd 1: Placebo 40mg PF-03463275 then Pd 2: Placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-03463275 Active Dose #1 | Subjects randomized to this arm will receive the following: Period 1) Active dose 60mg PF-03463275, then Period 2) Placebo. |
| FG001 | PF-03463275 Active Dose #2 | Subjects randomized to this arm will receive the following: Period 1) Active dose 40mg PF-03463275, then Period 2) Placebo. |
| FG002 | Placebo, Active Dose #1 | Subjects randomized to this arm will receive the following: Period 1) Placebo, then Period 2) Active Dose 60mg PF-03463275. |
| FG003 | Placebo, Active Dose #2 | Subjects randomized to this arm will receive the following: Period 1) Placebo, then Period 2) Active Dose 40mg PF-03463275. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 of Study |
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| ||||||||||||||||||
| Period 2 of Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-03463275 Active Dose #1 | Subjects randomized to this arm will receive the following: Period 1) Active dose 60mg PF-03463275, then Period 2) Placebo. |
| BG001 | PF-03463275 Active Dose #2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The 3 arms that subjects can be randomized to are: A) Period 1: Active 60mg PF-03463275 then Period 2: Placebo; B) Period 1: Active 40mg PF-03463275 then Period 2: Placebo; C) Period 1: Placebo then Period 2: Active 60mg or 40mg PF-03463275. The following completed both period 1 and period 2 of the study: A) 15 subjects; B) 21 subjects; and C) 18 subjects (11 randomized to period 1-placebo/period 2-60mg PF-03463275; and 8 randomized to period 1-placebo/period 2-40mg PF-03463275). | Posted | Mean | Standard Deviation | score on scale | Change from baseline in cognitive measures at approximately 5 weeks. Mean scores were calculated per time point for each arm. |
Adverse events were captured from the time at which the participant signed consent throughout their completion in the study (follow up visit after the completion of period 2), over a time period of approximately 4 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-03463275 Active Dose #1 | AEs while taking PF-03463275 Active Dose #1 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization from Intent to Overdose on Meds / Suicidal Ideation | Social circumstances | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased Anxiety | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christina Luddy | Yale University | 203-932-5711 | 4549 | christina.luddy@yale.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 28, 2021 | May 28, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 28, 2021 | May 28, 2021 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 12, 2018 | May 27, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| C549926 | 1-methyl-1H-imidazole-4-carboxylic acid (3-chloro-4-fluoro-benzyl)-(3-methyl-3-aza-bicyclo(3.1.0) hex-6-ylmethyl)amide |
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| Drug |
|
| Change from Baseline at approximately 1 week |
| West Haven |
| Connecticut |
| 06516 |
| United States |
| Physician Decision |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
Subjects randomized to this arm will receive the following: Period 1) Active dose 40mg PF-03463275, then Period 2) Placebo.
| BG002 | Placebo, Active Dose #1 | Subjects randomized to this arm will receive the following: Period 1) Placebo, then Period 2) Active dose 60mg PF-03463275. |
| BG003 | Placebo, Active Dose #2 | Subjects randomized to this arm will receive the following: Period 1) Placebo, then Period 2) Active dose 40mg PF-03463275. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
| Secondary | Alteration in Symptom Domain Scores and Event Related Potentials (ERPs) With PF-03463275 | To determine whether PF-03463275 impacts symptom domain scores and visual event related potentials (ERPs), analogous to long-term potentiation (LTP) with PF-03463275 treatment. A more positive value reflects a better outcome - there is no established range to report. A Z-score of 0 indicates the mean score. A positive z-score indicates the mean is higher than average. | Noncompleters and unusable data of completers led to differences between the total number of participants and the sample for this outcome measure. | Posted | Mean | Standard Error | Mean LTP Standard (z) Score +1 SE | Change from Baseline at approximately 1 week |
|
|
|
| 34 |
| 0 |
| 34 |
| 13 |
| 34 |
| EG001 | PF-03463275 Active Dose #2 | AEs while taking PF-03463275 Active Dose #2 | 0 | 33 | 2 | 33 | 13 | 33 |
| EG002 | Placebo | AEs while taking Placebo | 0 | 63 | 0 | 63 | 9 | 63 |
| EG003 | Washout | AEs while in the washout period (no medication) | 0 | 59 | 0 | 59 | 7 | 59 |
| Hospitalization Due to Stroke | General disorders | Systematic Assessment |
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| Blurry Vision | General disorders | Systematic Assessment |
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| Sleep Disturbance | General disorders | Systematic Assessment |
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| Hand Tremor | General disorders | Systematic Assessment |
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| Lightheadedness | General disorders | Systematic Assessment |
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| High Blood Pressure | Cardiac disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Sprained Ankle | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Foul Smelling Odor in Urine | Renal and urinary disorders | Systematic Assessment |
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| Bell's Palsy | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| GI Discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Bruised Forearms | General disorders | Systematic Assessment |
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| Elevated AST/ALT | Cardiac disorders | Systematic Assessment |
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| Knee Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Dry Cough | General disorders | Systematic Assessment |
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| Lower Back Strain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Hot Flashes | General disorders | Systematic Assessment |
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| Reduced Appetite | Gastrointestinal disorders | Systematic Assessment |
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| Whiplash | General disorders | Systematic Assessment |
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| Trigeminal Neuralgia | Nervous system disorders | Systematic Assessment |
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| Vertigo | General disorders | Systematic Assessment |
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| Orthostatic Hypotension | Cardiac disorders | Systematic Assessment |
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| Common Cold | General disorders | Systematic Assessment |
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| Tooth Pulled | General disorders | Systematic Assessment |
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| Stomach Cramps/Discomfort | General disorders | Systematic Assessment |
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| Foot Injury | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Increased Sleep | General disorders | Systematic Assessment |
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| Nausea / Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Laryngitis | General disorders | Systematic Assessment |
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| Vasovagal Response | General disorders | Systematic Assessment |
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| Hyperglycemia | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Dehydration | General disorders | Systematic Assessment |
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| Increase in Pain as a Result of Spinal Surgery Prior to Study | General disorders | Systematic Assessment |
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| Suicidal Ideation Due to Psychosocial Stressors | Psychiatric disorders | Systematic Assessment |
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| Reduced Sleep | General disorders | Systematic Assessment |
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| Upper Respiratory Infection | General disorders | Systematic Assessment |
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| Pharyngeal Pain | General disorders | Systematic Assessment |
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| Increased Appetite | General disorders | Systematic Assessment |
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| Increase in Pre-Existing Headache | General disorders | Systematic Assessment |
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| Productive Cough / Chest Congestion | General disorders | Systematic Assessment |
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| Increase in Fibromyalgia Pain | General disorders | Systematic Assessment |
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| Eye Sensitivity | General disorders | Systematic Assessment |
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| Intermittent Blurred Vision | General disorders | Systematic Assessment |
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| Paronychia (Right Middle Finger) | General disorders | Systematic Assessment |
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| Low Mood | Psychiatric disorders | Systematic Assessment |
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| Increased Urination | Renal and urinary disorders | Systematic Assessment |
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| Decreased Sleep (Associated with Pre-Existing Sleep Apnea) | General disorders | Systematic Assessment |
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| Increased Discomfort Associated with Pre-Existing Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Acute Ear Pain | General disorders | Systematic Assessment |
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| Intermittent Dental Pain | General disorders | Systematic Assessment |
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| Gum Soreness (at site of tooth extraction) | General disorders | Systematic Assessment |
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| Throat Pain | General disorders | Systematic Assessment |
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| Sore Shoulder | General disorders | Systematic Assessment |
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| Cold Symptoms | General disorders | Systematic Assessment |
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| Contact Dermatitis on Forehead | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Stiffness | General disorders | Systematic Assessment |
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| Light Sensitivity | General disorders | Systematic Assessment |
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| Hip Pain (associated with pre-existing bone spur) | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Pneumonia in Right Lung | General disorders | Systematic Assessment |
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| Sinus Congestion | General disorders | Systematic Assessment |
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| Wrist Drop / Radial Nerve Palsy | General disorders | Systematic Assessment |
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| Front Tooth Pain | General disorders | Systematic Assessment |
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| Post-Dose Period 1 |
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| Pre-Dose Period 2 |
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| Post-Dose Period 2 |
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