PF-06412562 · program
PF-06412562 (CVL-562) for Schizophrenia
PF-06412562 (CVL-562), a selective D1/D5 partial agonist, studied for cognitive impairment in schizophrenia. Pfizer's Phase 1b study in 95 psychiatrically stable patients on antipsychotics (NCT02418819; 3, 9 or 45 mg twice daily for 15 days) found the drug safe and well tolerated but showed no benefit over placebo on the MATRICS working-memory composite, reward-related striatal fMRI activation or 2-back accuracy; the 45 mg group improved significantly less than placebo on working memory (p=0.038).
Development timeline
- Results of the Yale-led TRANSCENDS Phase 2 target-engagement study of CVL-562 in early-course schizophrenia posted to ClinicalTrials.gov.
- Trial (portion) completedTRANSCENDS Phase 2 study of CVL-562 completes
- Yale-led, NIMH-funded Phase 2 target-engagement study TRANSCENDS (NCT04457310) of CVL-562 in early-course schizophrenia started; Cerevel Therapeutics is a collaborator.
- Trial startedYale-led Phase 2 TRANSCENDS study of CVL-562 in early-course schizophrenia starts
- missedPhase 1b of PF-06412562 in stable schizophrenia: safe and well tolerated, but no benefit over placebo on working memory, reward processing or 2-back accuracy over 15 days.↗
- NCT02418819 completed October 2016 (month precision); published results showed no benefit over placebo on cognition or reward processing.
- Trial terminatedPfizer terminates healthy-volunteer study of PF-06412562 for a business decision
- Pfizer Phase 1b study B7441007 (NCT02418819) in psychiatrically stable patients with schizophrenia started April 2015 (month precision on the registry).
Readouts
- 2025-10-15ReportedRegistry resultsNCT04457310
Results of the Yale-led TRANSCENDS Phase 2 target-engagement study of CVL-562 in early-course schizophrenia posted to ClinicalTrials.gov.
- 2019-07-02ReportedFull resultsmissedNCT02418819
Phase 1b of PF-06412562 in stable schizophrenia: safe and well tolerated, but no benefit over placebo on working memory, reward processing or 2-back accuracy over 15 days. ↗
Clinical trials in Schizophrenia
NCT044573102000027506Phase 2Completedn=112
A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia
NCT02418819B7441007Phase 1Completedn=103
A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia
metsafetySafety and tolerability (adjunctive to antipsychotics)
Adjunctive PF-06412562 was safe and well tolerated in patients with schizophrenia over 15 days.
missedprimaryChange from baseline in anterior ventral striatum BOLD activation (Monetary Incentive Delay, cue gain > cue no gain) on Day 15
No PF-06412562 dose differed significantly from placebo.
missedprimaryChange from baseline to Day 13 in MATRICS working-memory composite (0.038 (45 mg worse than placebo))
Working memory improved in all groups; the 45 mg group improved least and significantly less than placebo (two-sided p=0.038). No dose showed benefit over placebo.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| PF-06412562 oral tablet (immediate- and modified-release) Schizophrenia Phase 1b (NCT02418819): 3, 9 or 45 mg twice daily as modified-release tablets for 15 days. Yale Phase 2 (NCT04457310): single doses of 1, 4, 15 and 25 mg vs placebo before fMRI sessions. A healthy-volunteer study (NCT02201511) compared modified-release tablets (3 mg; 2 x 15 mg fasted and fed) with a 10 mg immediate-release tablet. | Oral | Twice daily | — |
Mechanism of action
Orally bioavailable, non-catechol, selective partial agonist at dopamine D1 and D5 receptors (Gs-coupled class-A GPCRs). The clinical hypothesis is that moderate D1/D5 stimulation in prefrontal cortex improves working memory and other cognitive functions that are impaired in schizophrenia, without the poor bioavailability and pharmacokinetics that limited earlier catechol D1 agonists.
| Target | Action | Affinity |
|---|---|---|
| D1primaryDRD1 | Partial agonist | —ⓘ |
| D5DRD5 | Partial agonist | —ⓘ |
← Full PF-06412562 compound page (identity, identifiers, all indications)
Sources
- Arce E, et al. 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 — Journal of Psychopharmacology / PubMed
- Evaluation of D1/D5 Partial Agonist PF-06412562 in Parkinson's Disease following Oral Administration. Neurodegener Dis. 2018 — Neuro-degenerative Diseases / PubMed
- NCT02306876 (B7441004) - PF-06412562 in healthy males (terminated, Pfizer business decision) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT02418819 (B7441007) - Phase 1b study of PF-06412562 in psychiatrically stable subjects with schizophrenia — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT04457310 - A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (CVL-562) — ClinicalTrials.gov (U.S. National Library of Medicine)