A Phase 2 interventional study of PF-04457845 and Placebo in Post-Traumatic Stress Disorder, sponsored by Pfizer. Terminated at 3 sites in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2016-06-29.
Sponsored by Pfizer · Phase 2, Interventional, and Treatment
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.
1,147 studies on the registry are indexed under Stress Disorders, Traumatic; 108 are open to participants now.
This study's enrollment of 14 is below the median of 60 across 908 interventional studies indexed under Stress Disorders, Traumatic.
Browse Stress Disorders, Traumatic studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
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Exclusion Criteria:
Drug: PF-04457845
Drug: Placebo
4mg PF-04457845 tablet taken once daily for 7 days.
Matching placebo tablet taken once daily for 7 days.
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.
Time frame: Baseline, Day 8
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.
Time frame: Baseline, Day 2
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline up to Day 18
| Milestone | PF-04457845 | Placebo |
|---|---|---|
| Started | 8 | 6 |
| Completed | 8 | 6 |
| Not completed | 0 | 0 |
Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala.
No measurements were reported for this outcome.
Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm.
No measurements were reported for this outcome.
Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task.
No measurements were reported for this outcome.
Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.
No measurements were reported for this outcome.
The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.
| participants | PF-04457845 | Placebo |
|---|---|---|
| Number of Participants With Abnormal Physical Examination Findings | 0 | 0 |
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.
| participants | PF-04457845 | Placebo |
|---|---|---|
| Number of Participants with AEs | 6 | 4 |
| Number of Participants with SAEs | 0 | 0 |
| Number of Participants Discontinued Due to AEs | 0 | 0 |
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.
| participants | PF-04457845 | Placebo |
|---|---|---|
| Total neutrophils <0.8 times lower limit of normal | 1 | 0 |
| Urine positive for nitrite | 1 | 0 |
| Urine positive for leukocyte esterase | 0 | 1 |
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.
| participants | PF-04457845 | Placebo |
|---|---|---|
| Supine SBP <90 mmHg | 0 | 0 |
| Standing SBP <90 mmHg | 0 | 0 |
| Supine DBP <50 mmHg | 0 | 0 |
| Standing DBP <50 mmHg | 0 | 0 |
| Supine Pulse Rate <40 or >120 bpm | 0 | 0 |
| Standing Pulse Rate <40 or >140 bpm | 0 | 0 |
| Supine SBP >=30 mmHg Increase From Baseline | 0 | 0 |
| Standing SBP >=30 mmHg Increase From Baseline | 0 | 1 |
| Supine DBP >=20 mmHg Increase From Baseline | 1 | 0 |
| Standing DBP >=20 mmHg Increase From Baseline | 0 | 0 |
| Supine SBP >=30 mmHg Decrease From Baseline | 0 | 0 |
| Standing SBP >=30 mmHg Decrease From Baseline | 0 | 0 |
| Supine DBP >=20 mmHg Decrease From Baseline | 0 | 0 |
| Standing DBP >=20 mmHg Decrease From Baseline | 1 | 1 |
ECG criteria of potential clinical concern were QTc absolute value \>=450 milliseconds (msec) or QTc absolute change \>=30 msec.
| participants | PF-04457845 | Placebo |
|---|---|---|
| QTcF Interval 450-<480 msec | 0 | 0 |
| QTcF Interval 480-<500 msec | 0 | 0 |
| QTcF Interval >=500 msec | 0 | 0 |
| QTcF Interval >=30 msec Increase From Baseline | 0 | 0 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PF-04457845 | — | — | 6/8 (75%) |
| Placebo | — | — | 4/6 (66.7%) |
| Event | PF-04457845 | Placebo |
|---|---|---|
| HeadacheNervous system disorders | 4/8 | 3/6 |
| DizzinessNervous system disorders | 2/8 | 0/6 |
| NauseaGastrointestinal disorders | 1/8 | 1/6 |
| Chest discomfortGeneral disorders | 0/8 | 1/6 |
| FatigueGeneral disorders | 0/8 | 1/6 |
| Post procedural haematomaInjury, poisoning and procedural complications | 0/8 | 1/6 |
| MigraineNervous system disorders | 0/8 | 1/6 |
| Sleep paralysisNervous system disorders | 0/8 | 1/6 |
| PalpitationsCardiac disorders | 1/8 | 0/6 |
| Abdominal discomfortGastrointestinal disorders | 1/8 | 0/6 |
| Age, Continuous(Years) | PF-04457845 | Placebo | Total |
|---|---|---|---|
| Mean | 35.6 ± 11.4 | 36.2 ± 15.1 | 35.9 ± 12.6 |
| Sex: Female, Male(Participants) | PF-04457845 | Placebo | Total |
|---|---|---|---|
| Female | 5 | 4 | 9 |
| Male | 3 | 2 | 5 |
This study is terminated, as verified in May 2016. You cannot join it, but the record below documents what was studied.
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