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The study stopped based on Pfizer portfolio prioritization and not due to safety and/or efficacy concern or change in benefit:risk assessment of PF-04457845.
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The purpose of the study is to evaluate proof of mechanism of PF-04457845, using a well-established neuroimaging paradigm including behavioral tasks selected to activate neuro-circuitry relevant to Post Traumatic Stress Disorder. It is hypothesized that PF-04457845 will modulate the Blood-oxygen-level dependent Functional Magnetic Resonance Imaging signal from the relevant neuro-circuits in patients with Post Traumatic Stress Disorder.
This is a Phase II, randomized, placebo-controlled, parallel group design study in male and female subjects with moderate-to-severe Post Traumatic Stress Disorder between the ages of 18 and 60 years old. During this study, a dose of 4 mg PF-04457845 will be administered in the morning on Days 1-7. On Each subject will undergo a resting state fMRI (pre and post and day 8), a fearful vs. neutral faces fMRI task and a fear extinction fMRI paradigm. The Emotional Faces Paradigm and resting state tasks will be performed on Day 1 (prior to drug or placebo) and on Day 8. Acquisition of fear conditioning will be performed during the first imaging session on Day 1. After the first imaging session on Day 1, subjects will complete behavioral rating scales and then be dosed. Approximately six hours after dosing subjects will re-enter the scanner and perform the fear extinction paradigm. On Day 2, subjects will perform the fear extinction memory retention task within the scanner. Further physiological monitoring, including skin conductance and heart rate, will take place during the fear extinction paradigm. One safety follow-up visit will occur between Days 11-18.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-04457845 | Drug | 4mg PF-04457845 tablet taken once daily for 7 days. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging fMRI) Percent Signal Change in Fearful Versus Neutral Face Contrast in Bilateral Amygdala | Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala. | Baseline, Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC) | Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm. | Baseline, Day 2 |
| Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical and Translational Science Institute (CTSI) | New York | New York | 10016 | United States | ||
| NYU CTSI Research Pharmacy (Drug Shipment Address) |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-04457845 | PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7. |
| FG001 | Placebo | Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-04457845 | PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7. |
| BG001 | Placebo | Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 From Baseline Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging fMRI) Percent Signal Change in Fearful Versus Neutral Face Contrast in Bilateral Amygdala | Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala. | There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to Good Clinical Practice (GCP) non-compliance that resulted in data integrity and quality issues. | Posted | Baseline, Day 8 |
|
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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-04457845 | PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C560620 | N-pyridazin-3-yl-4-(3-((5-(trifluoromethyl)pyridin-2-yl)oxy)benzylidene)piperidine-1-carboxamide |
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| Placebo |
| Drug |
Matching placebo tablet taken once daily for 7 days. |
|
Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task. |
| Baseline, Day 8 |
| Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala | Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task. | Baseline, Day 8 |
| Number of Participants With Abnormal Physical Examination Findings | The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems. | Baseline to up to Day 18 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last study drug administration that were absent before treatment or that worsened relative to pretreatment state. AEs included non-serious AEs and SAEs. | Baseline up to 28 days after last study drug administration (Day 35) |
| Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern | The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes; liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); chemistry (glucose); urinalysis (dipstick) (urine pH, urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine nitrite, urine leukocyte esterase); urinalysis microscopy (urine red blood cell, urine white blood cell, urine bacteria). Only parameters with abnormal values were reported. | Baseline up to Day 18 |
| Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern | Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of >=30 millimeters of mercury (mmHg) change from baseline or SBP <90 mmHg; diastolic blood pressure (DBP) >=20 mmHg change from baseline or DBP <50 mmHg. | Baseline up to Day 18 |
| Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern | ECG criteria of potential clinical concern were QTc absolute value >=450 milliseconds (msec) or QTc absolute change >=30 msec. | Baseline up to Day 18 |
| New York |
| New York |
| 10016 |
| United States |
| NYU School of Medicine | New York | New York | 10016 | United States |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7. |
|
| Secondary | Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC) | Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm. | There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues. | Posted | Baseline, Day 2 |
|
|
| Secondary | Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala | Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task. | There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues. | Posted | Baseline, Day 8 |
|
|
| Secondary | Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala | Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task. | There were no efficacy evaluations done in this study because of a change in the planned analysis after the study was prematurely terminated due to GCP non-compliance that resulted in data integrity and quality issues. | Posted | Baseline, Day 8 |
|
|
| Secondary | Number of Participants With Abnormal Physical Examination Findings | The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems. | The safety analysis population included all participants who received study medication. | Posted | Number | participants | Baseline to up to Day 18 |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last study drug administration that were absent before treatment or that worsened relative to pretreatment state. AEs included non-serious AEs and SAEs. | The safety analysis population included all participants who received study medication. | Posted | Number | participants | Baseline up to 28 days after last study drug administration (Day 35) |
|
|
|
| Secondary | Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern | The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes; liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); chemistry (glucose); urinalysis (dipstick) (urine pH, urine glucose, urine protein, urine blood, urine ketones, urine bilirubin, urine nitrite, urine leukocyte esterase); urinalysis microscopy (urine red blood cell, urine white blood cell, urine bacteria). Only parameters with abnormal values were reported. | The safety analysis population included all participants who received study medication. | Posted | Number | participants | Baseline up to Day 18 |
|
|
|
| Secondary | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern | Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of >=30 millimeters of mercury (mmHg) change from baseline or SBP <90 mmHg; diastolic blood pressure (DBP) >=20 mmHg change from baseline or DBP <50 mmHg. | The safety analysis population included all participants who received study medication. | Posted | Number | participants | Baseline up to Day 18 |
|
|
|
| Secondary | Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern | ECG criteria of potential clinical concern were QTc absolute value >=450 milliseconds (msec) or QTc absolute change >=30 msec. | The safety analysis population included all participants who received study medication. | Posted | Number | participants | Baseline up to Day 18 |
|
|
|
| 0 |
| 0 |
| 6 |
| 8 |
| EG001 | Placebo | Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7. | 0 | 0 | 4 | 6 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
|
| Post procedural haematoma | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Sleep paralysis | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Affect lability | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Flashback | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
|
| Post-traumatic stress disorder | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
|
Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Number of Participants Discontinued Due to AEs |
|
| Urine positive for leukocyte esterase |
|
| Supine DBP <50 mmHg |
|
| Standing DBP <50 mmHg |
|
| Supine Pulse Rate <40 or >120 bpm |
|
| Standing Pulse Rate <40 or >140 bpm |
|
| Supine SBP >=30 mmHg Increase From Baseline |
|
| Standing SBP >=30 mmHg Increase From Baseline |
|
| Supine DBP >=20 mmHg Increase From Baseline |
|
| Standing DBP >=20 mmHg Increase From Baseline |
|
| Supine SBP >=30 mmHg Decrease From Baseline |
|
| Standing SBP >=30 mmHg Decrease From Baseline |
|
| Supine DBP >=20 mmHg Decrease From Baseline |
|
| Standing DBP >=20 mmHg Decrease From Baseline |
|
| QTcF Interval >=500 msec |
|
| QTcF Interval >=30 msec Increase From Baseline |
|