PF-06412562 / Pfizer, AbbVie - LARVOL DELTA

A Translational Neuroscience & Computational Evaluation of a D1R Partial Agonist for Schizophrenia (TRANSCENDS): Rationale and Study Design of a Brain-Based Clinical Trial. (PubMed, medRxiv) - "Specifically, this study will assess whether the D1R/D5R partial agonist CVL-562 induces a dose-dependent engagement of spatial working memory circuits in schizophrenia using fMRI...This ensures high-standards for regulatory compliance, data quality, and data sharing across sites, improving aspects of current clinical trial data management. We share the study design and approach with the goal of advancing future pro-cognitive drug development and strategies for developing mechanistically-driven biomarkers in psychiatry."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (clinicaltrials.gov) - P1/2 | N=112 | Completed | Sponsor: Yale University | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Mar 2024

Trial completion • Trial completion date • CNS Disorders • Psychiatry • Schizophrenia

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (clinicaltrials.gov) - P1/2 | N=120 | Active, not recruiting | Sponsor: Yale University | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2024 ➔ Mar 2024

Enrollment closed • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Dopamine D Agonists: First Potential Treatment for Late-Stage Parkinson's Disease. (PubMed, Biomolecules) - "We explored if a D dopamine agonist would have efficacy in LsPD using a double-blind placebo-controlled crossover phase Ia/b study comparing the D agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. These data suggest for the first time that there can be useful pharmacological intervention in LsPD patients using D agonists and also that caregiver perspectives with mixed method analyses may overcome limitations using methods common in early-stage patients. The results encourage future clinical studies and understanding of the most efficacious signaling properties of a D agonist for this population."

Journal • CNS Disorders • Movement Disorders • Palliative care • Parkinson's Disease

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Yale University | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. (PubMed, Schizophr Bull) - "Newer drugs have recently become available, and these must be tested in the context of carefully designed paradigms that address methodological challenges. In this paper, we discuss how a better understanding of these challenges has shaped our proposed experimental design for testing a new D1R/D5R partial agonist, PF-06412562, renamed CVL-562."

Journal • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (clinicaltrials.gov) - P1/2; N=120; Recruiting; Sponsor: Yale University; Not yet recruiting ➔ Recruiting; Trial completion date: Nov 2022 ➔ Nov 2023; Initiation date: Nov 2020 ➔ Feb 2021; Trial primary completion date: Nov 2022 ➔ Nov 2023

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (clinicaltrials.gov) - P1/2; N=120; Not yet recruiting; Sponsor: Yale University; Initiation date: Aug 2020 ➔ Nov 2020

Trial initiation date • Alzheimer's Disease • CNS Disorders • Psychiatry • Schizophrenia

Effects of PF-06412562 on Value-based Decision-making in Healthy Individuals (clinicaltrials.gov) - P1; N=120; Completed; Sponsor: University of Zurich; Enrolling by invitation ➔ Completed

Clinical • Trial completion

The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study. (PubMed, J Parkinsons Dis) - P1 | "PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs."

Journal • CNS Disorders • Hypotension • Movement Disorders • Parkinson's Disease • Renal Disease

A novel approach to evaluate the pharmacodynamics of a selective dopamine D1/D5 receptor partial agonist (PF-06412562) in patients with stable schizophrenia. (PubMed, J Psychopharmacol) - "PF-06412562 failed to show clinical benefit relative to placebo on assessments of cognition or reward processing in symptomatically stable patients over a 15-day treatment period. Numerous limitations due to the safety study design warrant further efficacy evaluation for this drug mechanism."

Clinical • Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (clinicaltrials.gov) - P1/2; N=120; Not yet recruiting; Sponsor: Yale University

New P1/2 trial • Alzheimer's Disease • CNS Disorders • Schizophrenia

[VIRTUAL] THE ORAL D1/D5 PARTIAL AGONIST PF 06412562 IS SAFE AND TOLERATED IN ADVANCED-TO-END STAGE PARKINSON’S PATIENTS (AAT-ADPD 2020) - "The global clinical impression of change and mixed methods analyses favored PF‑06412562 over levodopa in 4 out of 5 participants who completed the study. Conclusions This phase Ib clinical trial demonstrated that PF-06412562 was safe, well tolerated, and that D1 agonists may improve quality of life in advPD patients."

Clinical

A Neurofunctional Domains Approach to Evaluate D1/D5 Dopamine Receptor Partial Agonism on Cognition and Motivation in Healthy Volunteers With Low Working Memory Capacity. (PubMed, Int J Neuropsychopharmacol) - P1b; "PF-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 Identifier: NCT02306876."

Clinical • Journal • MRI

Dopaminergic D Receptor Stimulation Affects Effort and Risk Preferences. (PubMed, Biol Psychiatry) - "The current results provide evidence that D receptor stimulation causally affects core aspects of cost-benefit decision making in humans."

Journal

Evaluation of D1/D5 Partial Agonist PF-06412562 in Parkinson's Disease following Oral Administration. (PubMed, Neurodegener Dis) - "We report the first evidence of potential anti-parkinsonian efficacy of the oral selective D1/D5 partial agonist PF-06412562 without the significant acute changes in cardiovascular parameters reported with previous D1 agonists."

Journal

PF 06412562 in Subjects With Advanced Stage Parkinson's Disease (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: Milton S. Hershey Medical Center; Active, not recruiting ➔ Completed; Trial completion date: Dec 2019 ➔ Apr 2019; Trial primary completion date: Dec 2019 ➔ Mar 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date

PF 06412562 in Subjects With Advanced Stage Parkinson's Disease (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: Milton S. Hershey Medical Center; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2019 ➔ Dec 2019; Trial primary completion date: Mar 2019 ➔ Dec 2019

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

D1 Receptor Occupancy (RO) Following a Single Dose of PF-06412562 (clinicaltrials.gov) - P1; N=6; Completed; Sponsor: Invicro; Active, not recruiting ➔ Completed; Trial completion date: Aug 2019 ➔ Mar 2019; Trial primary completion date: Aug 2019 ➔ Mar 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date

D1 Receptor Occupancy (RO) Following a Single Dose of PF-06412562 (clinicaltrials.gov) - P1; N=6; Active, not recruiting; Sponsor: Invicro; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

PF 06412562 in Subjects With Advanced Stage Parkinson's Disease (clinicaltrials.gov) - P1; N=8; Recruiting; Sponsor: Milton S. Hershey Medical Center; Trial completion date: Dec 2018 ➔ Mar 2019; Trial primary completion date: Dec 2018 ➔ Mar 2019

Clinical • Trial completion date • Trial primary completion date