SchizophreniaPhase 2NCT03557931
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
A Phase 2 study testing ASP4345, risperidone and quetiapine in people with Schizophrenia, run by Astellas Pharma Global Development, Inc. at 27 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- ASP4345, risperidone and quetiapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 233 participants
- Where
- 27 sitesUnited States
- Study dates
- 13 Jul 2018to 21 Oct 2019
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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, cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, history of seizure disorder, renal and/or other major disease or malignancy
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- Subject has any clinically significant abnormality of the physical examination, electrocardiogram (ECG) and clinical laboratory tests at screening or at admission to the study (day 1)
- Subject has known kidney disease and a glomerular filtration rate (GFR) < 60 mL/min per meter squared at screening and subjects will be discontinued from treatment only for decreases in the GFR that are clinically relevant
- Subject has a resting systolic blood pressure > 180 mmHg or < 90 mmHg, and a resting diastolic blood pressure > 100 mmHg at screening. These assessments may be repeated once, after a reasonable time period, at the investigator's discretion (but within the screening period)
- Subject has a mean corrected QTcF > 450 msec (for male subjects) and > 470 msec (for female subjects) at screening or at randomization. If the mean QTcF exceeds the limits above, one additional triplicate ECG can be taken on day 1
- Subject has a history in the 6 months prior to screening of consuming more than 14 units of alcoholic beverages per week for males and more than 7 units of alcoholic beverages per week for females. (Note 1 unit = 12 ounces of beer, 4 ounces of wine, or 1 ounce of spirits)
- Subject is currently using prohibited medications and is unable to washout, including over-the-counter products and agrees not to consume grapefruit and/or grapefruit juice
- Subject is currently using clozapine for treatment of schizophrenia
- Subject has a positive test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M) (anti-HAV [IgM]) or hepatitis C virus antibodies (anti- HCV) at Screening or has history of a positive test for human immunodeficiency virus type 1(HIV-1) and/or type 2 (HIV-2)
- Subject who has had electroconvulsive therapy within the 6 months prior to screening.
- Subject has a history of head injury with clinically significant sequelae, including loss of consciousness for 1 hour or greater
- Subject has received investigational study drug within 28 days or 5 half-lives, whichever is longer, prior to screening
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
United States27 sites
Albuquerque Neuroscience Inc.
Albuquerque, New Mexico, 87109
Michigan Clinical Research Institute PC
Ann Arbor, Michigan, 48105
Radiant Research, Inc.
Atlanta, Georgia, 30328
Atlanta Center for Medical Research
Atlanta, Georgia, 30331
Community Clinical Research, Inc.
Austin, Texas, 78754
Hassman Research Institute
Berlin, New Jersey, 08009
SPRI Clinical Trials, LLC
Brooklyn, New York, 11235
CNS Research Science, Inc.
Cerritos, California, 90703
Alam Medical Research Inc.
Chicago, Illinois, 60612
Uptown Research Institute
Chicago, Illinois, 60640
Midwest Clinical Research Center
Dayton, Ohio, 45417
InSite Clinical Research, LLC
DeSoto, Texas, 75115
Collaborative Neuroscience Network, LLC
Garden Grove, California, 92845
Cherry Street Services, Inc.
Grand Rapids, Michigan, 49503
CNS Research Science, Inc.
Jamaica, New York, 11432
Synergy East
Lemon Grove, California, 91945
New York State Psychiatric Institute
New York, New York, 10032
Manhattan Psychiatric Center's 125th Street Clinic
New York, New York, 10035
Pacific Research Partners, LLC
Oakland, California, 94607
California Neuropsychopharmacology Clinical Research Institute-LA, LLC
Pico Rivera, California, 90660
Pillar Clinical Research, LLC
Richardson, Texas, 75080
Finger Lakes Clinical Research
Rochester, New York, 14618
California Neuropsychopharmacology Clinical Research Institute, LLC (CNRI-San Diego)
San Diego, California, 92102
Artemis Institute for Clinical Research
San Diego, California, 92103
Sharp Mesa Vista Hospital
San Diego, California, 92123
Arch Clinical Trials, LLC
St Louis, Missouri, 63118
Collaborative Neuroscience Network, LLC
Torrance, California, 90502
About this study
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Parallel-group 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
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.
Read the detailed description
Participants received oral doses of ASP4345 or matching placebo QD (once daily) for 12 weeks. All participants were administered the first dose of blinded study drug at the site following randomization and provided with web-based applications that provided supplemental cognitive training and recorded treatment compliance. Participants returned to the clinic weekly for safety, efficacy, and/or pharmacokinetic procedures. Participants continued the participant's antipsychotic treatment for the entire study and were followed for 14 days after the participant's last dose of study drug.
- Conditions
- Schizophrenia
- Being tested
- ASP4345, placebo, risperidone, quetiapine, olanzapine
- Keywords
- aripiprazole, ziprasidone, lurasidone, schizophrenia, ASP4345, quetiapine, olanzapine, brexpiprazole, risperidone, paliperidone
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP4345Drug
oral administration
placeboDrug
oral administration
risperidoneDrug
Also called Risperdal
oral or depot administration
quetiapineDrug
Also called Seroquel
oral administration
olanzapineDrug
Also called Zyprexa
Oral or depot administration
ziprasidoneDrug
Also called Geodon
Oral or depot administration
aripiprazoleDrug
Also called Abilify
Oral or depot administration
brexpiprazoleDrug
Also called Rexulti
Oral administration
paliperidoneDrug
Also called Invega
Oral or depot administration
lurasidoneDrug
Also called Latuda
Oral administration
| Study group | Role | What they receive |
|---|---|---|
| ASP4345 50 milligram (mg) | Experimental | Participants on stable doses of antipsychotic medication received ASP4345 50 mg, capsules, orally, once daily for 12 weeks. Receives: Drug: ASP4345; Drug: risperidone; Drug: quetiapine; Drug: olanzapine; Drug: ziprasidone; Drug: aripiprazole; Drug: brexpiprazole; Drug: paliperidone; Drug: lurasidone |
| ASP4345 150 mg | Experimental | Participants on stable doses of antipsychotic medication received ASP4345 150 mg, capsules, orally, once daily for 12 weeks. Receives: Drug: ASP4345; Drug: risperidone; Drug: quetiapine; Drug: olanzapine; Drug: ziprasidone; Drug: aripiprazole; Drug: brexpiprazole; Drug: paliperidone; Drug: lurasidone |
| Placebo | Placebo comparator | Participants on stable doses of antipsychotic medication received ASP4345 placebo matching capsules, orally, once daily for 12 weeks. Receives: Drug: placebo; Drug: risperidone; Drug: quetiapine; Drug: olanzapine; Drug: ziprasidone; Drug: aripiprazole; Drug: brexpiprazole; Drug: paliperidone; Drug: lurasidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB neurocognitive composite score is a standardized mean of the six domain scores (excluding social cognition). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher score indicates less impairment.
Measured: Baseline and week 12/end of treatment (EoT)
Number of Participants With Adverse Event (AE)
Treatment emergent adverse event (TEAE) is defined as an AE observed after starting administration of the study drug and 28 days after the last dose of study drug. A study drug-related TEAE is defined as any TEAE with at least possible relationship to study treatment as assessed by the investigator or with missing assessment of the causal relationship. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, metabolic parameters etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant.
Measured: Baseline up to end of study (EoS) (week 14)
Number of Participants With Clinically Significant Differences in Columbia-Suicide Severity Rating Scale (C-SSRS) Values
The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses are provided to items 1 to 5 for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods [not plan] without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and items 6 to 10 for suicide behavior (6. Preparatory acts or behavior, 7. Aborted attempt, 8. Interrupted attempt, 9. Actual attempt, 10. Completed suicide).
Measured: Baseline up to EoS (week 14)
Number of Participants With Clinically Significant Differences in Abnormal Involuntary Movement Scale (AIMS) Values
AIMS is a 14-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 to 14 are yes/no questions regarding the global judgement and dental status of the participant. The total score is the sum of the scores for the 14 items and the possible total score ranges from 0 to 44. A higher total score is indicative of more severe dyskinetic movements.
Measured: Baseline, week 6 and week 12
Number of Participants With Clinically Significant Differences in Simpson Angus Scale (SAS) Values
SAS scale consists of 10 items including 7 items that address bradykinesia-rigidity and additional single items for tremor, glabellar tap, and salivation. Each item represents a specific physical condition and is rated on a 5-point category rating scale ranging from 0 (complete absence of the condition) to 4 (the condition is present to an extreme degree).The total score is obtained by adding the scores for the 10 individual items making the maximum possible score is 40. Higher scores are indicative of more severe Parkinsonian-type symptoms.
Measured: Baseline, week 6 and week 12
Number of Participants With Clinically Significant Differences in Barnes Akathisia Rating Scale (BARS) Values
BARS is used to rate observable, restless movements of drug induced akathisia and subjective awareness of restlessness and any distress associated with the akathisia. BARS consists of the following 4 items: objective assessment of akathisia symptoms, subjective assessment of the participants's awareness of inner restlessness, distress restlessness, and global clinical assessment of akathisia. First three items are rated on a 4-point scale ranging from 0 (no abnormal movements or absence of inner restlessness or no distress) to 3 (severe akathisia or awareness of intense compulsion to move most of the time or severe distress). The last item, the global clinical assessment of akathisia, is rated on a 6-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia). Total BARS score ranges from 0 to 14 with a higher score representing worse results.
Measured: Baseline, week 6 and week 12
Secondary outcomes (2)
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
The UPSA-2-ER assesses the functional abilities of the participant with schizophrenia in 6 domains: household management, communication, financial skills, transportation, comprehension/planning and medication management. The UPSA-2-ER total score has a range from 0 to 105. A higher score indicates less impairment.
Measured: Baseline and week 12/EoT
Concentration at Trough Level (Ctrough) for ASP4345
Ctrough concentration for ASP4345 was reported.
Measured: Predose: day 7, day 14, day 21, day 42 and day 84/EoT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start13 Jul 2018
- Primary completion21 Oct 2019
- Study completion21 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Executive Medical Director, Study director, Astellas Pharma Global Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03557931
- Sponsor's protocol ID
- 4345-CL-0015
- Status last verified
- Oct 2024
- First submitted
- 5 Jun 2018
- Last updated
- 12 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
Desai A, Benner L, Wu R, Gertsik L, Uz T, Marek GJ, Zhu T. Pharmacokinetics of ASP4345 from Single Ascending-Dose and Multiple Ascending-Dose Phase I Studies. Clin Pharmacokinet. 2021 Jan;60(1):79-88. doi: 10.1007/s40262-020-00911-0.
PubMed 32533536