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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02216097

Enrollment

Registered

2014-08-13

Start date

2014-10-31

Completion date

2015-03-31

Last updated

2016-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Post-Traumatic Stress Disorder

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.

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.

Interventions

DRUGPF-04457845

4mg PF-04457845 tablet taken once daily for 7 days.

DRUGPlacebo

Matching placebo tablet taken once daily for 7 days.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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, 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

Measure	Time frame	Description
Change From Baseline in BOLD fMRI Percent Activation in Bilateral Ventromedial Pre-Frontal Cortex (vmPFC)	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.
Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Right Amygdala	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.
Change From Baseline in BOLD fMRI Percent Signal Change in Fearful Versus Neutral Face Contrast in Left Amygdala	Baseline, Day 8	Difference measured in BOLD fMRI percent signal change in the left amygdala in fearful versus neutral faces during face processing task.
Number of Participants With Post-Baseline Electrocardiogram (ECG) Values Meeting Criteria of Potential Clinical Concern	Baseline up to Day 18	ECG criteria of potential clinical concern were QTc absolute value \>=450 milliseconds (msec) or QTc absolute change \>=30 msec.
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs	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.
Number of Participants With Clinical Laboratory Values Meeting Criteria for Potential Clinical Concern	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.
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern	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.
Number of Participants With Abnormal Physical Examination Findings	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
PF-04457845 PF-04457845 4 milligrams (mg) was orally administered once daily in the morning on Days 1 to 7.	8
Placebo Placebo matched to PF-04457845 was orally administered once daily in the morning on Days 1 to 7.	6
Total	14

Baseline characteristics

Characteristic	PF-04457845	Placebo	Total
Age, Continuous	35.6 Years STANDARD_DEVIATION 11.4	36.2 Years STANDARD_DEVIATION 15.1	35.9 Years STANDARD_DEVIATION 12.6
Sex: Female, Male Female	5 Participants	4 Participants	9 Participants
Sex: Female, Male Male	3 Participants	2 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	6 / 8	4 / 6
serious Total, serious adverse events	0 / 0	0 / 0

Outcome results

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.

Time frame: Baseline, Day 8

Population: 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.

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.

Time frame: Baseline, Day 2

Population: 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.

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.

Time frame: Baseline, Day 8

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.

Time frame: 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.

Time frame: Baseline to up to Day 18