A Study To Assess the Effects Of PF-04457845 On BOLD fMRI In Subjects With Post Traumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT02216097
• Recruitment Status: Terminated
• First Posted: August 13, 2014
• Results First Posted: April 8, 2016
• Last Update Posted: June 29, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Post-Traumatic Stress Disorder	Drug: PF-04457845; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo Controlled, Parallel Group Phase 2 Study To Assess Effects Of Pf 04457845 On Bold Functional Mri In Subjects With Ptsd
• Study Start Date: October 2014
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: March 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment	Drug: PF-04457845; 4mg PF-04457845 tablet taken once daily for 7 days.
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo tablet taken once daily for 7 days.

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Baseline, Day 8 ]
   Baseline BOLD fMRI percent signal change measured from baseline in fearful versus neutral face contrast during the emotional face processing task in bilateral amygdala.

Secondary Outcome Measures :

1. Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC) [ Time Frame: Baseline, Day 2 ]
   Difference measured in BOLD fMRI percent activation in the bilateral vmPFC during the fear extinction recall phase of the fear extinction paradigm.
2. Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala [ Time Frame: Baseline, Day 8 ]
   Difference measured in BOLD fMRI percent signal change in the right amygdala in fear versus neutral faces during the emotional face processing task.
3. Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala [ Time Frame: Baseline, Day 8 ]
   Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.
4. Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Baseline to up to Day 18 ]
   The full physical examination included head, ears, eyes, nose, mouth, skin, heart, and lung examinations, lymph nodes, gastrointestinal, skeletal, and neurological systems.
5. Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs [ Time Frame: Baseline up to 28 days after last study drug administration (Day 35) ]
   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.
6. Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern [ Time Frame: Baseline up to Day 18 ]
   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.
7. Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern [ Time Frame: Baseline up to Day 18 ]
   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.
8. Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern [ Time Frame: Baseline up to Day 18 ]
   ECG criteria of potential clinical concern were QTc absolute value >=450 milliseconds (msec) or QTc absolute change >=30 msec.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and women 18-60 years of age with a primary psychiatric diagnosis of Post Traumatic Stress Disorder

Exclusion Criteria:

• Other psychiatric illness requiring current treatment with medication.

Contacts and Locations

Locations

United States, New York

Clinical and Translational Science Institute (CTSI)

New York, New York, United States, 10016

NYU CTSI Research Pharmacy (Drug Shipment Address)

New York, New York, United States, 10016

NYU School of Medicine

New York, New York, United States, 10016

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02216097
• Other Study ID Numbers: B0541013
• First Posted: August 13, 2014
• Results First Posted: April 8, 2016
• Last Update Posted: June 29, 2016
• Last Verified: May 2016

Additional relevant MeSH terms:

Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders