A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia

A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, SPONSOR OPEN, PHASE 1B STUDY TO EXAMINE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF PF-06412562 IN PSYCHIATRICALLY STABLE SUBJECTS WITH SCHIZOPHRENIA

This study is designed to investigate the safety, tolerability pharmacokinetics and pharmacodynamic effects of PF-06412562 following multiple dose administration as MR tablets in subjects with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Other: Placebo; Drug: PF-06412562 3mg BID; Drug: PF-06412562 9mg BID; Drug: PF-06412562 45mg BID

Detailed Description

B7441007 is a randomized, double-blind, placebo-controlled, sponsor open, parallel group design, Phase 1b study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of 3 doses of PF-06412562 (3 mg BID, 9 mg BID and 45 mg BID) over 15 days in approximately 100 psychiatrically stable (as defined by the inclusion and exclusion criteria) subjects with schizophrenia are on background treatment with SOC antipsychotics and other psychotropic medications.

All doses will be administered twice daily, with approximately 12 hours between each dose.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91007
      • Arcadia MRI & Imaging Center
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group
    • Glendale, California, United States, 91206
      • Glendale Adventist Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21228
      • Maryland Psychiatric Research Center (MPRC) of the University of Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health, LLC
    • Rockville, Maryland, United States, 20850
      • Foers Long Term Care Pharmacy LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with schizophrenia both male and female
2. Evidence of stable schizophrenia symptomatology for at least 3 months (no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of symptoms of schizophrenia, etc).
3. Subjects must be in ongoing maintenance antipsychotic therapy other than clozapine (oral or depot) on a stable medication treatment regimen for for at least 2 months prior to Day 1, including concomitant psychotropic medications.

Exclusion Criteria:

1. History of seizure
2. Pregnant or nursing females
3. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of screening and at the time of dosing).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo BID	Other: Placebo; Placebo
Experimental: PF-06412562 3mg; PF-06412562 3mg BID	Drug: PF-06412562 3mg BID; PF-06412562; Other Names: PF-06412562 3mg
Experimental: PF-06412562 9mg; PF-06412562 9mg BID	Drug: PF-06412562 9mg BID; PF-06412562; Other Names: PF-06412562 9mg
Experimental: PF-06412562 45mg; PF-06412562 45mg BID	Drug: PF-06412562 45mg BID; PF-06412562; Other Names: PF-06412562 45mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity were counted as treatment emergent. AEs included both serious and non-serious AEs.	Baseline up to 7-10 days after last dose of study drug, up to 26 days
Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria	Vital Signs tests included systolic and diastolic blood pressure (BP) and pulse rate of seated supine and standing . Vital signs categorical summarization criteria were 1), supine and standing BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), supine and standing pulse rate <40 or greater than (>) 120 beats per minute (bpm).	Baseline up to 7-10 days after last dose of study drug, up to 26 days
Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria	ECG categorical summarization criteria were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): more than or equal to (>=) 200 milliseconds (msec); for percent change(PChg), >=25 percent (%) increase when baseline (b)>100 msec; or increase >=50% when b less than or equal to (<=)100 msec; 2), the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval): >=300 msec; >=25percent (%) increase when b >200 msec; or increase >=50% when b <=200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec and >=500 msec; increase from b >=30 - <60 and >=60 msec	Baseline up to 7-10 days after last dose of study drug, up to 26 days
Number of Participants With Blood and Urine Safety Laboratory Test Abnormalities	The total number of participants with blood and urine laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.	Baseline up to Day 15
Number of Participants With New Onset and Worsening of Post Baseline Suicidality in Columbia Suicide Severity Rating Scale (C-SSRS) on Day 1, Day 7 and Follow-up.	The C-SSRS was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. Versions were available for Screening/Baseline and follow-up visits. Post-baseline suicidality was displayed without regard to baseline and as new onset or worsening relative to baseline. A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment. A participant was considered to have a worsening of suicidality if the participant moved to a lower numbered Columbia Classification Algorithm of Suicide Assessment (C-CASA) category (observed in categories 1-4) than was reported at baseline.	Baseline, Days 1,7 and follow-up (7-10 days after last dose of study drug, up to 26 days)
Change From Baseline to Day 13 of Wechsler Memory Scale (WMS III) Spatial Span + Letter Number Span Composite Score (Working Memory Domain)	MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. Total score range of this subset ranges from 40 (minimum score) to 60 (maximum score), with higher scores indicating better cognitive function.	Baseline, Day 13
Change From Baseline in Blood Oxygen Level Dependent (BOLD) fMRI Activation Parameter Estimates (Z-scores) in Anterior Ventral Striatum Region of Interest (ROI) for the Contrast of Cue Gain > Cue No Gain in Monetary Incentive Delay (MID) Task on Day 15	MRI parameter estimates refer to the 90th percentile Z-statistics across all voxels within the Region of Interest (ROI). This task provided a measure of reward anticipation and reward consummation. One of 3 shapes was presented on the screen (each uniquely associated with gain, loss and neutral) as a cue, and participants were instructed to respond to each cue, using their dominant hand, by pressing in response to a subsequent target that appeared for a variable length of time. Baseline was defined as Day 0 assessment. To be included in analysis participants must have complete Monetary Incentive Delay (MID) data at both Baseline and post-baseline, without excessive head motion. Participants with MID <40% at baseline were excluded from the analysis and summary statistics. Scores were not bounded by a minimum or maximum range, higher z-score implies a greater motivation of the participant by the prospect of monetary gain than no monetary gain.	Baseline, Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of PF-06412562 for Each Dose.	PF-06412562 plasma concentration for each dose at 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16.	6, and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16
Plasma Concentrations of PF-06663872 at for Each Dose.	PF-06412562 plasma concentration for each dose at times 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16.	6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day16

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Arce E, Balice-Gordon R, Duvvuri S, Naylor M, Xie Z, Harel B, Kozak R, Gray DL, DeMartinis N. A novel approach to evaluate the pharmacodynamics of a selective dopamine D1/D5 receptor partial agonist (PF-06412562) in patients with stable schizophrenia. J Psychopharmacol. 2019 Oct;33(10):1237-1247. doi: 10.1177/0269881119855302. Epub 2019 Jul 2.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: April 13, 2015
• First Posted (Estimate): April 16, 2015

Study Record Updates

• Last Update Posted (Actual): February 4, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: B7441007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.