Clinical trial NCT02418819: A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-04-16
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 7-10 days after last dose of study drug, up to 26 days
measure: Number of Participants With Supine and Standing Vital Signs Meeting Categorical Summarization Criteria
timeFrame: Baseline up to 7-10 days after last dose of study drug, up to 26 days
measure: Number of Participants With Electrocardiogram (ECG) (Standard 12-Lead) Data Meeting Categorical Summarization Criteria
timeFrame: Baseline up to 7-10 days after last dose of study drug, up to 26 days
measure: Number of Participants With Blood and Urine Safety Laboratory Test Abnormalities
timeFrame: Baseline up to Day 15
measure: 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.
timeFrame: Baseline, Days 1,7 and follow-up (7-10 days after last dose of study drug, up to 26 days)
measure: Change From Baseline to Day 13 of Wechsler Memory Scale (WMS III) Spatial Span + Letter Number Span Composite Score (Working Memory Domain)
timeFrame: Baseline, Day 13
measure: 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
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Plasma Concentrations of PF-06412562 for Each Dose.
timeFrame: 6, and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16
measure: Plasma Concentrations of PF-06663872 at for Each Dose.
timeFrame: 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day16
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Arcadia MRI & Imaging Center
state: California
city: Glendale
country: United States
facility: California Clinical Trials Medical Group
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Baltimore
country: United States
facility: Maryland Psychiatric Research Center (MPRC) of the University of Maryland
state: Maryland
city: Gaithersburg
country: United States
facility: CBH Health, LLC
state: Maryland
city: Rockville
country: United States
facility: Foers Long Term Care Pharmacy LLC
state: Maryland
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.