Phase 2
Completed N=233
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
Source: ClinicalTrials.gov NCT03557931 ↗Enrolled (actual)
233
Serious AEs
2.2%
Results posted
Oct 2020
Primary outcomePrimary: Change From Baseline to Week 12/End of Treatment (EoT) in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score — 1.15; 1.34; 0.87 T-score — p=0.858
Summary
The purpose of this study was to evaluate the efficacy of ASP4345 on cognitive impairment compared to placebo using change from baseline in MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score (excluding social cognition domain). The primary estimand used a Hypothetical Strategy and compared participants as though the participant had continued on the assigned treatment and to evaluate the safety and tolerability of ASP4345 compared to placebo. This study also evaluated the effects of ASP4345 compared to placebo on functional capacity using the University of California San Diego Performance-based Skills Assessment-2 Extended Range (UPSA-2-ER) total score and evaluated the pharmacokinetic profile of ASP4345.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 12/End of Treatment (EoT) in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score |
1.15; 1.34; 0.87 | 0.858 |
| PRIMARY Number of Participants With Adverse Event (AE) |
45; 28; 28; 11; 13; 11 | — |
| PRIMARY Number of Participants With Clinically Significant Differences in Columbia-Suicide Severity Rating Scale (C-SSRS) Values |
0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Differences in Abnormal Involuntary Movement Scale (AIMS) Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Differences in Simpson Angus Scale (SAS) Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Differences in Barnes Akathisia Rating Scale (BARS) Values |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Change From Baseline to Week 12/EoT in University of California San Diego Performance-based Skills Assessment-2 Extended Range (UPSA-2-ER) Total Score |
3.11; 3.86; 2.56 | 0.639 |
| SECONDARY Concentration at Trough Level (Ctrough) for ASP4345 |
175.041; 483.84; 182.903; 428.88; 172.040; 384.48 | — |
Eligibility Criteria
Inclusion Criteria
- Subject has a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and confirmed by the Mini-International Neuropsychiatric Interview version 7.02
- Subject has a stable clinical course as suggested by the following:
- no psychiatric hospitalization within the last 4 months,
- no symptom-related changes in psychotropic medications (as defined in the concomitant medication section) within 4 weeks prior to baseline for oral medications and within 2 months for depot medications,
- and core positive symptoms no worse than moderate in severity and no evidence of a current severe major depressive episode (moderately severe depression is allowed)
- Subject has a stable living situation
- Subject's extrapyramidal symptoms are no worse than mild in severity
- Subject must be in ongoing maintenance (i.e., at least 4 weeks prior to day 1 for oral medications and within 2 months for depot medications) on up to 2 antipsychotic therapies (oral or depot) other than clozapine
- Subject has a body mass index range of 18.5 to 45.0 kg/m2
- Female subject must either:
- Be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without menses) prior to screening or
- Documented as surgically sterile
- Or, if of childbearing potential
- Agrees not to try to become pregnant during the study and for 28 days after the final study drug administration
- And has a negative blood pregnancy test at screening and a negative urine pregnancy test at day 1,
- and if heterosexually active, agrees to consistently use 1 form of highly effective birth control starting at screening and throughout the study period and for 28 days after the final study drug administration
- Female subjects must agree not to breastfeed starting at screening and throughout the study period, and for 28 days after the final study drug administration
- Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration
- A sexually active male subject with female partner(s) who is of childbearing potential is eligible if:
- Agrees to use male condom starting at screening and throughout the study period, and for 28 days after the final study drug administration
- Male subject must not donate sperm starting at screening and throughout the study period, and for 28 days after the final study drug administration
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 90 days after the final study drug administration
- Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form until completion of the last study visit
- Subject has a negative urine drug screen for drugs of abuse at screening and day 1, excluding cannabis and documented prescribed benzodiazepines
Exclusion Criteria
- Subject has a known or suspected hypersensitivity to ASP4345 or any components of the formulation
- Subject has had previous exposure with ASP4345
- Subject has a history of suicide attempt or suicidal behavior within 1 year prior to screening or has any suicidal ideation that meets criteria at a level of 4 or 5 by using the Columbia Suicide Severity Rating Scale (C-SSRS) or who is at significant risk to commit suicide
- Subject has any clinically significant liver chemistry test result (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) or a result > 1.5 times above the upper limit of normal (ULN) at screening or repeated within
1 week prior to potential randomization (day 1). In such a case, the assessment may be repeated once
- Subject has any history or evidence of any clinically significant allergic, cardiovasc
Data sourced from ClinicalTrials.gov (NCT03557931). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.