SchizophreniaPhase 1NCT03356639
A Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of ASP6981 in Subjects With Schizophrenia
A Phase 1 study testing ASP6981 in people with Schizophrenia, run by Astellas Pharma Global Development, Inc. at 2 sites in United States.
Trial summary
The primary purpose is to evaluate the safety and tolerability of ASP6981 in participants with schizophrenia. Also primary purpose is to evaluate the pharmacodynamics of ASP6981 in participants with schizophrenia as measured by cognitive function and neurophysiological biomarkers. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- ASP6981
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- 22 Jan 2018to 30 May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria.
- Subject is considered operationally stable if the subject has a low to moderate positive symptom score and moderate negative symptom score on the PANSS (Positive and Negative Syndrome Scale): no more than moderate rating on more than 2 PANSS items P1, P2, P3, P5, P6; no more than moderate severity rating for the negative items, N1, N2, N3, N4, N5, N6, N7; total PANSS score no more than 80.
- Subject must be in ongoing maintenance antipsychotic therapy (i.e., second generation antipsychotics other than clozapine oral or depot), on a stable (less than or equal to 25% change in dose) medication treatment regimen (approved oral or depot formulations of risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone; up to 2 permitted on condition that the second medication is not required to control treatment resistance or intractable psychotic symptoms) for more than or equal to 2 months for oral formulations or more than or equal to 3 months for depot formulations prior to screening, including concomitant psychotropic medications, such as, trazodone and zolpidem for sleep.
- Subject has a body mass index (BMI) range of 18.5 to 40.0 kg/m2, inclusive, and weighs at least 50 kg.
- Subject has a negative urine drug screen for drugs of abuse.
- Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.
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- Female subject must agree not to breastfeed 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 are of childbearing potential is eligible if:
- The male subject agrees to use a male condom starting at screening and continue throughout the study period and for 90 days after the final study drug administration.
- The male subject has not had a vasectomy or is not sterile, as defined above, their female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continuing throughout study treatment and for 90 days after the male subject receives their 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.
- Male subject must not donate sperm starting at screening and 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 ESV.
Who cannot join
- Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Subject has a known or suspected hypersensitivity to ASP6981 or any components of the formulation used.
- Subject has had previous exposure with ASP6981.
- Subject has a history of heavy smoking (use more than 40 cigarettes/2 packs per day) or a user of nicotine replacement therapy (includes nicotine patches, Chantix or similar therapeutic agents) in the past 3 months prior to admission to the clinical unit (day -3).
- Subject has a history of suicide attempt or suicidal behavior within 2 years prior to screening. Any suicidal ideation that meets criteria at a level of 4 or 5 by using C-SSRS within the last 3 months or who is at significant risk to commit suicide will be excluded.
- Subject has any clinically significant liver chemistry test result (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma glutamyl transferase, total bilirubin [TBL]) or a result greater than 1.5 x greater than upper limit of normal (ULN). In such a case, the assessment may be repeated once.
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- Subject has any history of allergic conditions deemed clinically significant.
- Subject has any history or evidence of any clinically significant cardiovascular, gastro-intestinal endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric (other than schizophrenia or schizoaffective disorder), renal and/or other major disease or malignancy.
- Subject has a history of being diagnosed with moderate or severe tardive dyskinesia, bipolar disorder, major depressive disorder, personality disorders, neuroleptic malignancy syndrome or anxiety disorder.
- Subject has any clinically significant abnormality of the physical examination, ECG and protocol-defined clinical laboratory tests.
- Subject has a mean pulse lower than 40 or greater than 100 bpm; resting systolic blood pressure (SBP) lower than 90 or greater than 180 mmHg, or a resting diastolic blood pressure (DBP) greater than 100 mmHg at screening and on day -3 (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically). If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken at screening and on day -3.
- Subject has a mean QT interval using Fridericia's correction (QTcF) of greater than 450 ms (for male subjects) and greater than 470 ms (for female subjects). If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken at screening and on day -3.
- Subject uses any prescribed (including current treatment with anticholinergic medications such as benztropine, biperiden, procyclidine, and trihexyphenidyl) or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., valerian) in the 2 weeks prior to study drug administration until the ESV, except for:
- Approved second generation antipsychotics (risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone), or
- Approved intermittent use of short-acting hypnotic agents trazodone or zolpidem (no less than 12 hours prior to dosing), or
- Approved intermittent use of anticholinergic compounds, or
- Approved use of concomitant medication for the treatment of hypertension, hyperlipidemia or diabetes mellitus, or
- Occasional use of acetaminophen (up to 2 g/day), or
- Hormonal contraceptives, or
- Hormone replacement therapy.
- Subject has a history of consuming more than: 14 units of alcoholic beverages per week for male subjects or 7 units of alcoholic beverages per week for female subjects within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol or drugs of abuse at screening or at admission to the clinical unit (day -3 of period 1). Subject tests positive for benzodiazepines at admission to the clinical unit (day -3 of period 1).
- Subject who is unable to refrain from smoking or drinking coffee for 3 hours prior to the Cogstate and EEG testing.
- Subject has used any strong CYP3A inhibitors (e.g., but not limited to: boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and/or has consumed grapefruit, grapefruit-containing products, Seville orange or Seville orange-containing products within 72 hours prior to admission to the clinical unit (day -3 of period 1).
- Subject regularly uses any inducer of CYP3A metabolism (e.g., but not limited to: carbamazepine, phenytoin, rifampin, St. John's Wort, bosentan, efavirenz, etravirine, modafinil, nafcillin, amprenavir, aprepitant, armodafinil, clobazamechinacea, pioglitazone, prednisone, rufinamide, vemurafenib) in the 3 months prior to admission to the clinical unit (day -3 of period 1).
- Subject has a positive serology test for hepatitis B surface antigen, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies or human immunodeficiency virus antibodies type 1 or 2.
- Subject who has had electroconvulsive therapy within the 6 months prior to screening.
- Subject has a history of seizures or of a condition with risk of seizures; as an exception, a history of 1 febrile seizure in childhood will not exclude a subject.
- Subject has a history of head injury with clinically significant sequelae.
- Subject experienced an acute exacerbation of schizophrenia requiring hospitalization or an increase in antipsychotic medication (with reference to drug or dose) within the last 2 months prior to screening.
- Subject has hearing loss, is unable to detect 1000 Hz tones presented at 40 dB.
- Subject has a condition which makes the subject unable to complete or perform the EEG assessments defined in the study (e.g., dreadlocks), during the study screening period.
- Subject has a history of spine surgery (with intact dura mater) in the past year and/or a history of brain and/or spinal cord injury.
- Subject has a condition which makes the subject unable to complete the study cognitive assessments defined in the study, during the study screening period.
- Subject has any condition, which makes the subject unsuitable for study participation.
- Subject has participated in any study or has been treated with any investigational drugs within 28 days or 5 half-lives whichever is longer, prior to screening.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Community Clinical Research
Austin, Texas, 78754
Cctmg/Parexel
Glendale, California, 91206
About this study
Official title: A Phase 1 Randomized, 2-way, Crossover Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of ASP6981 in Patients With Schizophrenia
The primary purpose is to evaluate the safety and tolerability of ASP6981 in participants with schizophrenia.
Also primary purpose is to evaluate the pharmacodynamics of ASP6981 in participants with schizophrenia as measured by cognitive function and neurophysiological biomarkers.
The secondary purpose of this study is to evaluate the pharmacokinetics of ASP6981 in participants with schizophrenia.
Read the detailed description
This study will evaluate ASP6981 in stable participants with schizophrenia on stable doses of up to 2 second generation antipsychotic drugs for at least 2 months prior to screening. Participants will be enrolled and randomized into 1 of 4 treatment sequences: AB, BA, CD, DC.
Screening period: After a screening period of up to 29 days prior to study drug administration, eligible participants will be admitted to the clinical unit on day -3.
Investigational period: Enrolled participants will be randomized to receive either ASP6981 or Placebo first and then will be crossed over to receive the opposite intervention. The study will consist of two treatment periods of 14 days separated by a washout period of 14 days. Participants will be discharged from the clinical unit on day 15 for the washout period. Washout may be extended up to a maximum of 21 days depending on the participant's availability.
Follow up: Participants will return to the clinical unit for an End of Study Visit (ESV) on day 28 of period 2 or, if the participant terminated early from the study, 14 days after the last dose of study drug.
- Conditions
- Schizophrenia
- Being tested
- ASP6981, Placebo
- Keywords
- Schizophrenia, ASP6981, Safety, Phase 1
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP6981Drug
Oral
PlaceboDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| ASP6981 50 mg, then matching Placebo | Experimental | Participants in Sequence AB will first receive ASP6981 capsules orally (50 mg) during period 1. After a 14-day washout period, participants receive matching placebo during period 2. Participants will receive ASP6981 capsules or matching placebo capsules every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, ASP6981 or matching placebo will be administered under fasting conditions. Receives: Drug: ASP6981; Drug: Placebo |
| Matching Placebo, then ASP6981 50 mg | Experimental | Participants in Sequence BA will first receive matching placebo capsules orally during period 1. After a 14-day washout period, participants receive ASP6981 capsules (50 mg) during period 2. Participants will receive matching placebo or ASP6981 capsules every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, matching placebo or ASP6981 will be administered under fasting conditions. Receives: Drug: ASP6981; Drug: Placebo |
| ASP6981 135 mg, then matching Placebo | Experimental | Participants in Sequence CD will first receive ASP6981 capsules orally (135 mg) during period 1. After a 14-day washout period, participants receive matching placebo during period 2. Participants will receive ASP6981 capsules or matching placebo every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, ASP6981 or matching placebo will be administered under fasting conditions. Receives: Drug: ASP6981; Drug: Placebo |
| Matching Placebo, then ASP6981 135 mg | Experimental | Participants in Sequence DC will first receive matching placebo capsules orally during period 1. After a-14 day washout period, participants receive ASP6981 (135 mg) during period 2. Participants will receive matching placebo or ASP6981 capsules every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, matching placebo or ASP6981 will be administered under fasting conditions. Receives: Drug: ASP6981; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability assessed by nature, frequency and severity of adverse events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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.
Measured: Up to End of Study (up to a maximum of 65 days)
Number of participants with vital signs abnormalities and/or adverse events related to treatment
Number of participants with potentially clinically significant vital sign values.
Measured: Up to End of Study (up to a maximum of 65 days)
Number of participants with laboratory value abnormalities and/or adverse events related to treatment
Number of participants with potentially clinically significant laboratory values.
Measured: Up to End of Study (up to a maximum of 65 days)
Safety and tolerability assessed by 12-lead electrocardiogram (ECG)
Routine 12 lead ECGs will be performed after the participant has been in a supine position for at least 5 minutes.
Any clinically significant adverse changes on the ECG will be reported as (serious) Adverse Event.
Measured: Up to End of Study (up to a maximum of 65 days)
Safety and tolerability assessed by C-SSRS
C-SSRS: Columbia - Suicide Severity Rating Scale. The C SSRS is a rating scale that assesses the full spectrum of suicidality: suicide ideation, intensity of ideation, suicidal behaviors and actual attempts.
Measured: Up to 50 days
Safety and tolerability assessed through metabolic parameter: waist circumference
Waist circumference will be summarized by ASP6981 treatment group and pooled placebo.
Measured: Up to End of Study (up to a maximum of 65 days)
Safety and tolerability assessed through metabolic parameter: lipid panel
Lipid panel will be summarized by ASP6981 treatment group and pooled placebo.
Measured: Up to End of Study (up to a maximum of 65 days)
Safety and tolerability assessed through metabolic parameter: glucose level
Glucose level will be summarized by ASP6981 treatment group and pooled placebo.
Measured: Up to End of Study (up to a maximum of 65 days)
Safety and tolerability assessed by weight
Weight to be summarized by ASP6981 treatment group and pooled placebo.
Measured: Up to End of Study (up to a maximum of 65 days)
Safety and tolerability assessed for movement disorder using AIMS
AIMS: Abnormal Involuntary Movement Scale. The AIMS aids in the early detection of tardive dyskinesia as well as providing a method for on going surveillance. The AIMS is a checklist and uses a 5 point rating scale for recording scores for 7 body areas: face, lips, jaw, tongue, upper extremities, lower extremities and trunk.
Measured: Up to 50 days
Safety and tolerability assessed for movement disorder using BARS
BARS: Barnes Akathisia Rating Scale. The BARS is a rating scale that is used to assess the severity of drug induced akathisia.
Measured: Up to 50 days
Safety and tolerability assessed for movement disorder using SAS
SAS: Simpson Angus Scale. The SAS is a 10 item scale used to rate adverse neurological effects of antipsychotic medications more broadly. It involves direct observation and a brief neurological examination. Rating requires the investigator to observe the participant's gait and check for tremor, excessive salivation and rigidity in the arms, shoulder and neck. Each item is rated from 0 to 4 and a total score can be obtained.
Measured: Up to 50 days
Pharmacodynamics (PD) of ASP6981 assessed through Cogstate: general composite score of executive function and memory cognitive testing
Cogstate testing composed by Groton Maze Learning, One Back, One Card and International Shopping List tests: specific Cogstate's panels for schizophrenia.
Measured: Day 14: period 1 and 2
PD of ASP6981 assessed through electroencephalogram (EEG): electrophysiological measures of P300 (P3a, P3b) and Mismatch Negativity (MMN)
EEG will be recorded after cognitive testing.
Measured: Day 14: period 1 and 2
Secondary outcomes (7)
Pharmacokinetics (PK) of ASP6981 and its metabolites, if necessary (plasma): Tmax
Tmax: time of maximum concentration
Measured: Day 1 and day 14: period 1 and 2
PK of ASP6981 and its metabolites, if necessary (plasma): Cmax
Cmax: maximum concentration
Measured: Day 1 and day 14: period 1 and 2
PK of ASP6981 and its metabolites, if necessary (plasma): AUC12
AUC12: Area under the concentration time curve from the time of dosing to 12 hours postdose
Measured: Day 1: period 1 and 2
PK of ASP6981 and its metabolites, if necessary (plasma): Ctrough
Ctrough: Concentration immediately prior to dosing at multiple dosing
Measured: Day 7 and day 14: period 1 and 2 and day 13 of period 2
PK of ASP6981 and its metabolites, if necessary (plasma): AUCtau
AUCtau: Area under the concentration time curve from the time of dosing to the start of the next dosing interval
Measured: Day 14: period 1 and 2
PD of ASP6981 assessed through Cogstate: composite score of attention cognitive testing
Cogstate testing composed by Detection Test and Identification.
Measured: Day 14: period 1 and 2
PD of ASP6981 assessed through EEG: electrophysiological measures of Auditory Steady State Response (ASSR), N100, P200 and resting state
EEG will be recorded after cognitive testing.
Measured: Day 14: period 1 and 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2017
- Study start22 Jan 2018
- Primary completion30 May 2018
- Study completion30 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Medical Director, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03356639
- Sponsor's protocol ID
- 6981-CL-0004
- Status last verified
- Oct 2024
- First submitted
- 28 Nov 2017
- Last updated
- 31 Oct 2024
- Results posted
- No
- 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/.
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Randomized, 2-way, Crossover Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of ASP6981 in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT03356639
- Acronym / sponsor ID
- 6981-CL-0004
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, ASP6981, Safety, Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Jan 2018 (actual)
- Primary completion
- 30 May 2018 (actual)
- Study completion
- 30 May 2018 (actual)
- First posted
- 29 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose is to evaluate the safety and tolerability of ASP6981 in participants with schizophrenia.
Also primary purpose is to evaluate the pharmacodynamics of ASP6981 in participants with schizophrenia as measured by cognitive function and neurophysiological biomarkers.
The secondary purpose of this study is to evaluate the pharmacokinetics of ASP6981 in participants with schizophrenia.
Detailed description
This study will evaluate ASP6981 in stable participants with schizophrenia on stable doses of up to 2 second generation antipsychotic drugs for at least 2 months prior to screening. Participants will be enrolled and randomized into 1 of 4 treatment sequences: AB, BA, CD, DC.
Screening period: After a screening period of up to 29 days prior to study drug administration, eligible participants will be admitted to the clinical unit on day -3.
Investigational period: Enrolled participants will be randomized to receive either ASP6981 or Placebo first and then will be crossed over to receive the opposite intervention. The study will consist of two treatment periods of 14 days separated by a washout period of 14 days. Participants will be discharged from the clinical unit on day 15 for the washout period. Washout may be extended up to a maximum of 21 days depending on the participant's availability.
Follow up: Participants will return to the clinical unit for an End of Study Visit (ESV) on day 28 of period 2 or, if the participant terminated early from the study, 14 days after the last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ASP6981 50 mg, then matching Placebo | Experimental | Drug: ASP6981, Drug: PlaceboParticipants in Sequence AB will first receive ASP6981 capsules orally (50 mg) during period 1. After a 14-day washout period, participants receive matching placebo during period 2. Participants will receive ASP6981 capsules or matching placebo capsules every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, ASP6981 or matching placebo will be administered under fasting conditions. |
| Matching Placebo, then ASP6981 50 mg | Experimental | Drug: ASP6981, Drug: PlaceboParticipants in Sequence BA will first receive matching placebo capsules orally during period 1. After a 14-day washout period, participants receive ASP6981 capsules (50 mg) during period 2. Participants will receive matching placebo or ASP6981 capsules every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, matching placebo or ASP6981 will be administered under fasting conditions. |
| ASP6981 135 mg, then matching Placebo | Experimental | Drug: ASP6981, Drug: PlaceboParticipants in Sequence CD will first receive ASP6981 capsules orally (135 mg) during period 1. After a 14-day washout period, participants receive matching placebo during period 2. Participants will receive ASP6981 capsules or matching placebo every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, ASP6981 or matching placebo will be administered under fasting conditions. |
| Matching Placebo, then ASP6981 135 mg | Experimental | Drug: ASP6981, Drug: PlaceboParticipants in Sequence DC will first receive matching placebo capsules orally during period 1. After a-14 day washout period, participants receive ASP6981 (135 mg) during period 2. Participants will receive matching placebo or ASP6981 capsules every 12 hours on days 1 through 14 (only in the morning of day 14) of period 1 and 2. On days 1 and 14 of period 1 and 2, matching placebo or ASP6981 will be administered under fasting conditions. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Subject has a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria.
- Subject is considered operationally stable if the subject has a low to moderate positive symptom score and moderate negative symptom score on the PANSS (Positive and Negative Syndrome Scale): no more than moderate rating on more than 2 PANSS items P1, P2, P3, P5, P6; no more than moderate severity rating for the negative items, N1, N2, N3, N4, N5, N6, N7; total PANSS score no more than 80.
- Subject must be in ongoing maintenance antipsychotic therapy (i.e., second generation antipsychotics other than clozapine oral or depot), on a stable (less than or equal to 25% change in dose) medication treatment regimen (approved oral or depot formulations of risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone; up to 2 permitted on condition that the second medication is not required to control treatment resistance or intractable psychotic symptoms) for more than or equal to 2 months for oral formulations or more than or equal to 3 months for depot formulations prior to screening, including concomitant psychotropic medications, such as, trazodone and zolpidem for sleep.
- Subject has a body mass index (BMI) range of 18.5 to 40.0 kg/m2, inclusive, and weighs at least 50 kg.
- Subject has a negative urine drug screen for drugs of abuse.
Key exclusion criteria (35 listed)
- Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Subject has a known or suspected hypersensitivity to ASP6981 or any components of the formulation used.
- Subject has had previous exposure with ASP6981.
- Subject has a history of heavy smoking (use more than 40 cigarettes/2 packs per day) or a user of nicotine replacement therapy (includes nicotine patches, Chantix or similar therapeutic agents) in the past 3 months prior to admission to the clinical unit (day -3).
- Subject has a history of suicide attempt or suicidal behavior within 2 years prior to screening. Any suicidal ideation that meets criteria at a level of 4 or 5 by using C-SSRS within the last 3 months or who is at significant risk to commit suicide will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASP6981Oral | Drug | ASP6981 135 mg, then matching Placebo, ASP6981 50 mg, then matching Placebo, Matching Placebo, then ASP6981 135 mg, Matching Placebo, then ASP6981 50 mg |
| PlaceboOral | Drug | ASP6981 135 mg, then matching Placebo, ASP6981 50 mg, then matching Placebo, Matching Placebo, then ASP6981 135 mg, Matching Placebo, then ASP6981 50 mg |
Primary outcome
Safety and tolerability assessed by nature, frequency and severity of adverse events (AEs)
Time frame: Up to End of Study (up to a maximum of 65 days)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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.
Number of participants with vital signs abnormalities and/or adverse events related to treatment
Time frame: Up to End of Study (up to a maximum of 65 days)
Number of participants with potentially clinically significant vital sign values.
Number of participants with laboratory value abnormalities and/or adverse events related to treatment
Time frame: Up to End of Study (up to a maximum of 65 days)
Number of participants with potentially clinically significant laboratory values.
Safety and tolerability assessed by 12-lead electrocardiogram (ECG)
Time frame: Up to End of Study (up to a maximum of 65 days)
Routine 12 lead ECGs will be performed after the participant has been in a supine position for at least 5 minutes. Any clinically significant adverse changes on the ECG will be reported as (serious) Adverse Event.
Safety and tolerability assessed by C-SSRS
Time frame: Up to 50 days
C-SSRS: Columbia - Suicide Severity Rating Scale. The C SSRS is a rating scale that assesses the full spectrum of suicidality: suicide ideation, intensity of ideation, suicidal behaviors and actual attempts.
Safety and tolerability assessed through metabolic parameter: waist circumference
Time frame: Up to End of Study (up to a maximum of 65 days)
Waist circumference will be summarized by ASP6981 treatment group and pooled placebo.
Safety and tolerability assessed through metabolic parameter: lipid panel
Time frame: Up to End of Study (up to a maximum of 65 days)
Lipid panel will be summarized by ASP6981 treatment group and pooled placebo.
Safety and tolerability assessed through metabolic parameter: glucose level
Time frame: Up to End of Study (up to a maximum of 65 days)
Glucose level will be summarized by ASP6981 treatment group and pooled placebo.
Safety and tolerability assessed by weight
Time frame: Up to End of Study (up to a maximum of 65 days)
Weight to be summarized by ASP6981 treatment group and pooled placebo.
Safety and tolerability assessed for movement disorder using AIMS
Time frame: Up to 50 days
AIMS: Abnormal Involuntary Movement Scale. The AIMS aids in the early detection of tardive dyskinesia as well as providing a method for on going surveillance. The AIMS is a checklist and uses a 5 point rating scale for recording scores for 7 body areas: face, lips, jaw, tongue, upper extremities, lower extremities and trunk.
Safety and tolerability assessed for movement disorder using BARS
Time frame: Up to 50 days
BARS: Barnes Akathisia Rating Scale. The BARS is a rating scale that is used to assess the severity of drug induced akathisia.
Safety and tolerability assessed for movement disorder using SAS
Time frame: Up to 50 days
SAS: Simpson Angus Scale. The SAS is a 10 item scale used to rate adverse neurological effects of antipsychotic medications more broadly. It involves direct observation and a brief neurological examination. Rating requires the investigator to observe the participant's gait and check for tremor, excessive salivation and rigidity in the arms, shoulder and neck. Each item is rated from 0 to 4 and a total score can be obtained.
Pharmacodynamics (PD) of ASP6981 assessed through Cogstate: general composite score of executive function and memory cognitive testing
Time frame: Day 14: period 1 and 2
Cogstate testing composed by Groton Maze Learning, One Back, One Card and International Shopping List tests: specific Cogstate's panels for schizophrenia.
PD of ASP6981 assessed through electroencephalogram (EEG): electrophysiological measures of P300 (P3a, P3b) and Mismatch Negativity (MMN)
Time frame: Day 14: period 1 and 2
EEG will be recorded after cognitive testing.
7 secondary outcomes
Pharmacokinetics (PK) of ASP6981 and its metabolites, if necessary (plasma): Tmax
Time frame: Day 1 and day 14: period 1 and 2
PK of ASP6981 and its metabolites, if necessary (plasma): Cmax
Time frame: Day 1 and day 14: period 1 and 2
PK of ASP6981 and its metabolites, if necessary (plasma): AUC12
Time frame: Day 1: period 1 and 2
PK of ASP6981 and its metabolites, if necessary (plasma): Ctrough
Time frame: Day 7 and day 14: period 1 and 2 and day 13 of period 2
PK of ASP6981 and its metabolites, if necessary (plasma): AUCtau
Time frame: Day 14: period 1 and 2
PD of ASP6981 assessed through Cogstate: composite score of attention cognitive testing
Time frame: Day 14: period 1 and 2
PD of ASP6981 assessed through EEG: electrophysiological measures of Auditory Steady State Response (ASSR), N100, P200 and resting state
Time frame: Day 14: period 1 and 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2024.
- Individual participant dataSharing planned: 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senior Medical Director study director
Astellas Pharma Global Development, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASP6981 in people with Schizophrenia, run by Astellas Pharma Global Development, Inc. at 2 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 13 inclusion and 35 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 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability assessed by nature, frequency and severity of adverse events (AEs) (time frame: Up to End of Study (up to a maximum of 65 days)). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2024.