ASP4345 / Astellas - LARVOL DELTA

A Study to Assess the Safety and Efficacy of ASP4345 as Add-on Treatment for Cognitive Impairment in Subjects With Schizophrenia on Stable Doses of Antipsychotic Medication (clinicaltrials.gov) - P2 | N=233 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P2a ➔ P2

Phase classification • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D receptor positive allosteric modulator in patients with schizophrenia. (PubMed, Neuropsychopharmacology) - P1 | "The findings need to be confirmed in studies with a larger patient population. Nonetheless, the trends in safety and pharmacodynamic data support further clinical development of ASP4345 for the treatment of CIAS."

Clinical • Journal • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Pain • Psychiatry • Schizophrenia • Suicidal Ideation

Pharmacokinetics of ASP4345 in Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Studies (SIRS 2019) - "There was less than dose proportional increase in exposures of ASP4345. Discussion These studies showed no effect of food on PK of ASP4345, less than dose proportionality and penetration of ASP4345 into the brain."

Late-breaking abstract • PK/PD data • CNS Disorders • Schizophrenia

Phase 1 Study on the Safety, Tolerability, and Pharmacodynamic Effects of ASP4345 for the Treatment of Cognitive Impairment in Patients with Schizophrenia (SIRS 2019) - "Discussion ASP4345 was generally well tolerated and showed evidence of CNS penetration via functional biomarkers in subjects with schizophrenia. Results support continued development of ASP4345 for CIAS."

Clinical • Late-breaking abstract • P1 data • PK/PD data • CNS Disorders • Schizophrenia

Dopamine Type 1 Receptor Positive Allosteric modulator, ASP4345 for the Treatment of Cognitive Impairment Associated with Schizophrenia (CIAS) (SIRS 2019) - P2a | "Based on these results Astellas continues the development of ASP4345 for the treatment of CIAS. Currently, we are running a proof of concept (POC) study testing safety and efficacy of ASP4345 as add-on treatment for CIAS in patients with schizophrenia on stable doses of antipsychotic medication (NCT03557931)."

CNS Disorders • Schizophrenia

Pharmacokinetics of ASP4345 from Single Ascending-Dose and Multiple Ascending-Dose Phase I Studies. (PubMed, Clin Pharmacokinet) - P1 | "The pharmacokinetics of ASP4345 suggest that single daily dosing is appropriate for ASP4345. Furthermore, the concentration of ASP4345 in cerebrospinal fluid compared to free drug concentrations in plasma provides evidence of penetration of ASP4345 into the brain."

Journal • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Schizophrenia

Evaluating Pro-Cognitive Properties of a Dopamine Type 1 Receptor Positive Allosteric Modulator, ASP4345, for the Treatment of Cognitive Impairment Associated with Schizophrenia (CIAS): A Randomized, Double-Blind, Placebo-Controlled, Proof of Concept (POC) Study in Subjects with Schizophrenia on Stable Doses of Antipsychotic Medication (SIRS 2020) - P2a | "Challenges with existing ligands in occupancy studies as well as limited clinical data with D1 PAMs make it difficult to connect functional markers with a clinical meaningful dose level. More translational and clinical studies with D1 PAMs are needed to better understand this relationship and in turn the role of D1 modulators in this field."

Clinical

A Study to Assess the Safety and Efficacy of ASP4345 as Add-on Treatment for Cognitive Impairment in Subjects With Schizophrenia on Stable Doses of Antipsychotic Medication (clinicaltrials.gov) - P2a; N=233; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Safety and Efficacy of ASP4345 as Add-on Treatment for Cognitive Impairment in Subjects With Schizophrenia on Stable Doses of Antipsychotic Medication (clinicaltrials.gov) - P2a; N=233; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed