This study will test whether CVL-562 (PF-06412562), a dopamine 1 partial agonist novel compound, affects working memory neural circuits in patients with early episode schizophrenia. The overall aim is to establish neuroimaging biomarkers of the Dopamine Receptor 1/Dopamine Receptor 5 Family (D1R/D5R) target engagement to accelerate development of D1R/D5R agonists in humans to treat cognitive impairments that underlie functional disability in schizophrenia, a key unaddressed clinical and public health concern.

Start Date02 Mar 2021

Sponsor / Collaborator

Yale University

[+5]

NCT03665454 / CompletedPhase 1IIT

A Phase Ib Safety, Tolerability, and Efficacy Study of Two Days of Oral Split Dose (25/20 mg) Administration of PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

The purpose of this study is to test the safety and tolerability of the investigational drug PF-06412562 compared to the current medical standard of care medication for Parkinson's disease, carbidopa/levodopa. This research also is being done to find out if the investigational drug PF-06412562 can help improve the motor (movement) function, alertness, and cognitive (thinking) skills of people who are considered to be in the advanced-stage of Parkinson's disease. In this study, PF06412562 is 'investigational,' which means that it is experimental and has not been approved by the US Food and Drug Administration (FDA), but can be used in clinical research studies such as this one.

Start Date24 Sep 2018

Sponsor / Collaborator

Hershey Medical Center

[+1]

NCT03686501 / CompletedEarly Phase 1

An Open-Label Study To Evaluate D1 Receptor Occupancy (RO) Following a Single Dose of PF-06412562, Using Positron Emission Tomography (PET) With Ligand [18F]MNI-968 in Healthy Male Subjects

To assess the D1 receptor occupancy (D1 RO) in striatum after a single oral administration of PF-06412562.

Start Date10 Sep 2018

Sponsor / Collaborator

Invicro LLC

100 Clinical Results associated with PF-06412562

100 Translational Medicine associated with PF-06412562

100 Patents (Medical) associated with PF-06412562

Literatures (Medical) associated with PF-06412562

27 Oct 2020·Journal of Parkinson's DiseaseQ3 · MEDICINE

The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson’s Disease: A Feasibility Study

Q3 · MEDICINE

Article

Author: Fernandez-Mendoza, Julio ; Mahoney, Susan E ; Delnomdedieu, Marielle ; Mailman, Richard B ; Kong, Lan ; Sun, Dongxiao ; Snyder, Bethany ; Miller, Amanda J ; Van Scoy, Lauren Jodi ; Harrington, William ; Gray, David L ; Duvvuri, Sridhar ; Huang, Xuemei ; Eslinger, Paul J ; Arnold, Amy C ; De Jesus, Sol ; Lewis, Mechelle M ; Wang, Xi

Background: Current drug treatments have little efficacy in advanced-to-end-stage Parkinson’s disease (advPD), yet there are no reports of interventional trials in advPD. D1 dopamine agonists have the potential to provide benefit. Objective: To determine the feasibility and safety of the selective D1/D5 dopamine partial agonist PF 06412562 in advPD. Methods: A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25 + 20 mg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers. Results: Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22 y). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n = 1, SoC: n = 0), moderate (PF-06412562: n = 1, SoC: n = 1), or severe but non-serious (PF-06412562: n = 3, SoC: n = 2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians’ and four participants per caregivers’ rating. Conclusion: PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs.

27 May 2020·International Journal of NeuropsychopharmacologyQ2 · MEDICINE

A Neurofunctional Domains Approach to Evaluate D1/D5 Dopamine Receptor Partial Agonism on Cognition and Motivation in Healthy Volunteers With Low Working Memory Capacity

Q2 · MEDICINE

ArticleOA

Author: Liu, Wenlei ; DeMartinis, Nicholas ; Harel, Brian T ; Balice-Gordon, Rita ; Park, Lovingly ; Xie, Zhiyong ; Honey, Garry D ; Duvvuri, Sridhar ; Arce, Estibaliz ; Chatham, Christopher ; Gray, David L ; Kozak, Rouba ; Naylor, Melissa Graham ; Braley, Gabriel H

AbstractBackgroundDopamine D1 receptor signaling plays key roles in core domains of neural function, including cognition and reward processing; however, many questions remain about the functions of circuits modulated by dopamine D1 receptor, largely because clinically viable, selective agonists have yet to be tested in humans.MethodsUsing a novel, exploratory neurofunctional domains study design, we assessed the safety, tolerability, pharmacodynamics, and pharmacokinetics of PF-06412562, a selective D1/D5R partial agonist, in healthy male volunteers who met prespecified criteria for low working memory capacity. Functional magnetic resonance imaging, electrophysiologic endpoints, and behavioral paradigms were used to assess working memory, executive function, and motivation/reward processing following multiple-dose administration of PF-06412562. A total of 77 patients were assigned PF-06412562 (3 mg twice daily and 15 mg twice daily) or placebo administered for 5 to 7 days. Due to the exploratory nature of the study, it was neither powered for any specific treatment effect nor corrected for multiple comparisons.ResultsNominally significant improvements from baseline in cognitive endpoints were observed in all 3 groups; however, improvements in PF-06412562–treated patients were less than in placebo-treated participants. Motivation/reward processing endpoints were variable. PF-06412562 was safe and well tolerated, with no serious adverse events, severe adverse events, or adverse events leading to dose reduction or temporary discontinuation except for 1 permanent discontinuation due to increased orthostatic heart rate.ConclusionsPF-06412562, in the dose range and patient population explored in this study, did not improve cognitive function or motivation/reward processing more than placebo over the 5- to 7-day treatment period.ClinicalTrials.gov IdentifierNCT02306876

01 Apr 2020·Biological PsychiatryQ1 · MEDICINE

Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences

Q1 · MEDICINE

Article

Author: Gray, David L ; de Martinis, Nicholas ; Tobler, Philippe N ; Kozak, Rouba ; Fehr, Ernst ; Soutschek, Alexander ; Gvozdanovic, Geraldine ; Duvvuri, Sridhar ; Jetter, Alexander ; Harel, Brian

BACKGROUNDActivation of D₁ receptors has been related to successful goal-directed behavior, but it remains unclear whether D₁ receptor activation causally tips the balance of weighing costs and benefits in humans. Here, we tested the impact of pharmacologically stimulated D₁ receptors on sensitivity to risk, delay, and effort costs in economic choice and investigated whether D₁ receptor stimulation would bias preferences toward options with increased costs in a cost-specific manner.METHODSIn a randomized, double-blind, placebo-controlled, parallel-group phase 1 study, 120 healthy young volunteers received either placebo or 1 of 3 doses (6 mg, 15 mg, or 30 mg) of a novel, selective D₁ agonist (PF-06412562). After drug administration, participants performed decision tasks measuring their preferences for risky, delayed, and effortful outcomes.RESULTSHigher doses of the D₁ agonist increased the willingness to exert physical effort for reward as well as reduced the preference for risky outcomes. We observed no effects on preferences for delayed rewards.CONCLUSIONSThe current results provide evidence that D₁ receptor stimulation causally affects core aspects of cost-benefit decision making in humans.

100 Deals associated with PF-06412562

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Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Phase 2	US	Pfizer Inc.	24 Jan 2021
Cognitive Dysfunction	Phase 2	CH	Pfizer Inc.	08 May 2017
Neurodegenerative Diseases	Phase 2	CH	Pfizer Inc.	08 May 2017
Parkinson Disease	Phase 2	US	Pfizer Inc.	01 Mar 2014

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02418819 (CTgov)	Phase 1	Schizophrenia	103	Placebo	(jxzirhqlzk) = pfcmmyeoyd chzxwowxsf (tnixyxsstj, cqqohmfoju - lohbwpxmhf) View more	-	04 Feb 2019

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