AzTrials
AzTrials

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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
Show all 25Show fewer
  • 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
Show all 17Show fewer
  • 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

Other trials in United States

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 groups in NCT03557931
Study groupRoleWhat they receive
ASP4345 50 milligram (mg)ExperimentalParticipants 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 mgExperimentalParticipants 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
PlaceboPlacebo comparatorParticipants 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.

  1. 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)

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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)

  1. 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

  2. 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.

  1. First posted15 Jun 2018
  2. Study start13 Jul 2018
  3. Primary completion21 Oct 2019
  4. Study completion21 Oct 2019

Resources

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)
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
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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline and week 12/end of treatment (EoT)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03557931, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in