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

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ClinicalTrials.gov Identifier: NCT02418819
Recruitment Status : Completed
First Posted : April 16, 2015
Results First Posted : February 4, 2019
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE March 23, 2015
First Posted Date  ICMJE April 16, 2015
Results First Submitted Date  ICMJE August 3, 2017
Results First Posted Date  ICMJE February 4, 2019
Last Update Posted Date February 4, 2019
Actual Study Start Date  ICMJE April 2015
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 7-10 days after last dose of study drug, up to 26 days ]
    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.
  • Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria [ Time Frame: Baseline up to 7-10 days after last dose of study drug, up to 26 days ]
    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).
  • Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria [ Time Frame: Baseline up to 7-10 days after last dose of study drug, up to 26 days ]
    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
  • Number of Participants With Blood and Urine Safety Laboratory Test Abnormalities [ Time Frame: Baseline up to Day 15 ]
    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.
  • 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. [ Time Frame: Baseline, Days 1,7 and follow-up (7-10 days after last dose of study drug, up to 26 days) ]
    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.
  • Change From Baseline to Day 13 of Wechsler Memory Scale (WMS III) Spatial Span + Letter Number Span Composite Score (Working Memory Domain) [ Time Frame: Baseline, Day 13 ]
    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.
  • 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 [ Time Frame: Baseline, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 13, 2015)
  • N-back (Working memory task) [ Time Frame: Change from baseline at Day 15 ]
    percent change from baseline ratio score of correct answers
  • Monetary Incentive Delay [ Time Frame: Change from baseline at Day 15 ]
    change in baseline in BOLD fMRI activation parameter estimates in right ventral striatum
  • Columbia Suicide Severity Rating Scale [ Time Frame: Change from baseline at Day 1, Day 7 and Follow-up ]
    Columbia Suicide Severity Rating Scale
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Plasma Concentrations of PF-06412562 for Each Dose. [ Time Frame: 6, and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16 ]
    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.
  • Plasma Concentrations of PF-06663872 at for Each Dose. [ Time Frame: 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day16 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2015)
Cavg: Average plasma PF- 06412562 and PF- 06663872 concentrations at steady state [ Time Frame: Day 0, 7, 12 and 16 ]
Average plasma PF- 06412562 and PF- 06663872 concentrations for each dose at times 6, and 12 hours on days 0, 7 and 12, as well as 0 hours on Day 16
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Schizophrenia
Intervention  ICMJE
  • Drug: PF-06412562 3mg BID
    PF-06412562
    Other Name: PF-06412562 3mg
  • Drug: PF-06412562 9mg BID
    PF-06412562
    Other Name: PF-06412562 9mg
  • Drug: PF-06412562 45mg BID
    PF-06412562
    Other Name: PF-06412562 45mg
  • Other: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: PF-06412562 3mg
    PF-06412562 3mg BID
    Intervention: Drug: PF-06412562 3mg BID
  • Experimental: PF-06412562 9mg
    PF-06412562 9mg BID
    Intervention: Drug: PF-06412562 9mg BID
  • Experimental: PF-06412562 45mg
    PF-06412562 45mg BID
    Intervention: Drug: PF-06412562 45mg BID
  • Placebo Comparator: Placebo
    Placebo BID
    Intervention: Other: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2019)
103
Original Estimated Enrollment  ICMJE
 (submitted: April 13, 2015)
100
Actual Study Completion Date  ICMJE October 2016
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02418819
Other Study ID Numbers  ICMJE B7441007
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP