SchizophreniaPhase 1NCT02720263
A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP4345 in Patients With Schizophrenia
A Phase 1 study testing ASP4345 in people with Schizophrenia, run by Astellas Pharma Global Development, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of multiple ascending oral doses of ASP4345 in patients with schizophrenia. In addition, this study will evaluate the pharmacokinetics of multiple ascending oral doses of ASP4345 in patients with schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- ASP4345
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2016to 8 Jun 2017
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient has a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria.
- A patient is considered operationally stable if the patient has a low to moderate positive symptoms score and moderate negative symptom score on the Positive and Negative Syndrome Scale (PANSS): No more than moderate rating on more than 2 PANSS items P1, P2, P3, P5, P6 (positive symptom section); No more than moderate severity rating for the negative items, N1, N2, N3, N4, N5, N6, N7 (negative symptom section); total PANSS score no more than 80.
- Patient must be in ongoing maintenance antipsychotic therapy other than clozapine (oral or depot), on a stable (≤ 25% change in dose) medication treatment regimen (approved oral or depot formulations of risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone) for ≥ 2 months for oral formulations or ≥ 3 months for depot formulations prior to screening, including concomitant psychotropic medications, such as, trazodone and zolpidem for sleep.
- Patient has a body mass index (BMI) range of 18.5 to 40.0 kg/m2, inclusive, and weighs at least 50 kg at screening.
- Female patient must be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
Show all 21Show fewer
- Documented surgically sterile (at least 1 month prior to screening defined as hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy)
- Female patient must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.
- Male patient and their female spouse/partners who are of childbearing potential must be using 2 forms of highly effective birth control† (1 of which must be a barrier method‡) starting at screening and continue throughout the study period and for 90 days after the final study drug administration.
- †Highly effective forms of birth control include:
- Consistent and correct usage of established oral contraception
- Injected or implanted hormonal methods of contraception
- Established intrauterine device or intrauterine system
- Bilateral tubal ligation
- Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments and complies with the preferred and usual lifestyle of the patient.
- ‡Barrier methods of birth control include:
- Condom with spermicidal foam/gel/film/cream/suppository
- Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
- Male patient must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
- Patient agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form until the end of study visit (ESV).
- Patient has a negative urine drug screen for drugs of abuse at screening and check in.
Who cannot join
- Female patient who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Patient has a known or suspected hypersensitivity to ASP4345 or any components of the formulation used.
- Patient has had previous exposure with ASP4345.
- Patient 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 at screening or at admission to the clinical unit (day 2) will be excluded.
- Patient 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 > than 1.5 times above the ULN at screening or at admission to the clinical unit (day 2). In such a case, the assessment may be repeated once.
- Patient has any history of allergic conditions deemed clinically significant.
Show all 34Show fewer
- Patient has any history or evidence of any clinically significant cardiovascular, gastrointestinal endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric (other than schizophrenia or schizoaffective disorder), renal and/or other major disease or malignancy. Patient has any condition, which, makes the patient unsuitable for clinical study participation.
- Patient has been diagnosed with moderate or severe tardive dyskinesia, bipolar disorder, major depressive disorder, personality disorders, neuroleptic malignancy syndrome or anxiety disorder.
- Patient has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to admission to the clinical unit (day 2).
- Patient has any clinically significant abnormality at screening or at admission to the clinical unit (day 2).
- Patient has a mean pulse < 40 or > 100 bpm; mean systolic blood pressure (SBP) > 160 mmHg; mean diastolic blood pressure (DBP) > 90 mmHg (vital signs measurements taken in triplicate after patient has been resting in supine position for 5 minutes; pulse will be measured automatically) at screening or at admission to the clinical unit (day 2). If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken on day 2.
- Patient has a mean QTcF > 440 msec (for male patients) and > 460 msec (for female patients) at screening or at admission to the clinical unit (day 2). If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken on day 2.
- Patient uses any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., Valerian) in the 2 weeks prior to study drug administration, except for:
- Approved antipsychotics (risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone), or
- Approved intermittent use of trazodone or zolpidem (no less than 12 hours prior to dosing), 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).
- Patient has a history of consuming more than 14 units of alcoholic beverages per week 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 patient tests positive for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or at admission to the clinical unit (day 2). A patient with a positive result for benzodiazepines may be included in this clinical study, if the result can be explained by the use of permitted concomitant medication.
- Patient 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 2).
- Patient has used any strong or moderate CYP2D6 inhibitors (e.g., but not limited to: bupropion, fluoxetine, paroxetine, quinidine, cinacalcet, duloxetine, terbinafine) within 72 hours prior to admission to the clinical unit (day 2).
- Patient regularly uses any inducer of metabolism (e.g., but not limited to: barbiturates, rifampin, St. John's Wort) in the 1 month prior to admission to the clinical unit (day 2).
- Patient has used any drugs of abuse within 3 months prior to admission to the clinical unit (day 2).
- Patient has had significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to admission to the clinical unit (day 2).
- Patient has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM]), hepatitis C virus (HCV) antibodies, or human immunodeficiency virus (HIV) antibodies type 1 or 2 at screening.
- Patient has participated in any clinical study or has been treated with any investigational drugs within 28 days or 5 half lives whichever is longer, prior to screening.
- Patient is an employee of the Astellas Group or Contract Research Organization (CRO) involved in the clinical study.
- Patient who has had electroconvulsive therapy within the 6 months prior to screening.
- Patient 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 patient.
- Patient has a history of head injury with clinically significant sequelae.
- Patient experienced an acute exacerbation of schizophrenia requiring hospitalization within the last 3 months.
- Patient experienced an acute exacerbation of schizophrenia requiring increase in antipsychotic medication (with reference to drug or dose) within the last 4 weeks.
- Patient has hearing loss, is unable to detect 1000 Hz tones presented at 40 dB.
- Patient has a hairstyle that would interfere with electroencephalogram (EEG) recording quality.
- Patient 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP4345 in Patients With Schizophrenia
The purpose of this study is to evaluate the safety and tolerability of multiple ascending oral doses of ASP4345 in patients with schizophrenia. In addition, this study will evaluate the pharmacokinetics of multiple ascending oral doses of ASP4345 in patients with schizophrenia.
- Conditions
- Schizophrenia
- Being tested
- ASP4345, Matching Placebo
- Keywords
- Schizophrenia, ASP4345
- 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
Matching PlaceboDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| Double-Blind ASP4345 Multiple Dose Levels | Experimental | ASP4345 will be administered orally as a single daily dose on days 1 through 14 with water. On days 1, 7, and 14, ASP4345 will be administered under fasting conditions. On days 2-6 and 8-13, ASP4345 will be administered under fed conditions. Receives: Drug: ASP4345 |
| Double-Blind Placebo Multiple Dose | Placebo comparator | Matching placebo capsules will be administered orally as a single daily dose on days 1 through 14 with water. On days 1, 7, and 14, matching placebo capsules will be administered with food. On days 2-6 and 8-13, matching placebo will be administered under fed conditions. Receives: Drug: Matching Placebo |
| Open-Label ASP4345 | Experimental | ASP4345 will be administered orally as a single daily dose on days 1 through 14 with water. On days 1, 7, and 14, ASP4345 will be administered with food. On days 2-6 and 8-13, ASP4345 will be administered under fed conditions. This is an optional cohort where subjects will be enrolled to further characterize pharmacodynamics in the event a higher sample size is necessary to determine changes in electrophysiological biomarkers. Receives: Drug: ASP4345 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability assessed as nature, frequency and severity of adverse events
Measured: Up to Day 21
Change from baseline in supine blood pressure as a measure of safety and tolerability
Measured: Baseline and Day 21
Change from baseline in pulse as a measure of safety and tolerability
Measured: Baseline and Day 21
Change from baseline in oral body temperature as a measure of safety and tolerability
Measured: Baseline and Day 21
Safety and tolerability assessed by an orthostatic challenge test
Incidence of positive orthostatic challenge tests will be summarized.
Measured: Up to Day 14
Number of participants with abnormal laboratory values and/or adverse events related to treatment
Clinical laboratory tests include hematology, biochemistry and urinalysis.
Measured: Up to Day 21
Safety and tolerability assessed by routine 12-lead electrocardiogram (ECG)
The overall interpretation of 12-lead electrocardiogram (ECG) results (normal, abnormal not clinically significant and abnormal clinically significant) will be summarized.
Measured: Up to Day 18
Safety and tolerability assessed by continuous 12-lead ECG recording
ECGs will be collected using a 12-lead ECG continuous monitoring system which records continuous digital data.
Measured: Up to Day 14
Safety and tolerability assessed by abuse liability using an Addiction Research Center Inventory (ARCI-49)
ARCI-49 is a 49-item short form standardized questionnaire for abuse potential liability.
Measured: Up to Day 17
Safety and tolerability assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a scale that assesses the full spectrum of suicidality: suicidal ideation, intensity of ideation, suicidal behaviors and actual attempts.
Measured: Up to Day 18
Safety and tolerability assessed by Bond-Lader Visual Analog Scale (VAS)
The VAS will be used to rate patients' feelings in terms of 16 dimensions. The dimensions will be presented as 100 mm lines, the 2 extremes of the emotion (i.e., alert - drowsy) written at each end.
Measured: Up to Day 17
Safety and tolerability assessed by metabolic syndrome: weight circumference
Measured: Up to Day 14
Safety and tolerability assessed by metabolic syndrome: cholesterol
Measured: Up to Day 21
Safety and tolerability assessed by metabolic syndrome: triglycerides
Measured: Up to Day 21
Safety and tolerability assessed by metabolic syndrome: glucose level
Measured: Up to Day 21
Safety and tolerability assessed by weight
Measured: Up to Day 14
Safety and tolerability assessed by movement disorder: Abnormal Involuntary Movement Scale (AIMS)
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 Day 14
Safety and tolerability assessed by movement disorder: Simpson Angus Scale (SAS)
The SAS is a 10-item scale used to rate adverse neurological effects of antipsychotic medications more broadly. Each item is rated from 0 to 4 and a total score will be obtained.
Measured: Up to Day 14
Safety and tolerability assessed by movement disorder: Barnes Akathisia Rating Scale (BARS)
The BARS is a rating scale used to assess the severity of drug-induced akathisia.
Measured: Up to Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): tlag
Time prior to the time corresponding to the first measurable (nonzero) concentration (tlag)
Measured: Day 1
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): tmax
Time of maximum concentration (tmax)
Measured: Day 1 and Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Cmax
Maximum concentration (Cmax)
Measured: Day 1 and Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): AUCtau
Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)
Measured: Day 1 and Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Ctrough
Concentration immediately prior to dosing at multiple dosing (Ctrough)
Measured: Days 2 through 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): t1/2
Terminal elimination half-life (t1/2)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): MRTinf
Mean residence time extrapolated to time infinity (MRTinf)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): terminal elimination rate constant
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Vz/F
Apparent volume of distribution during the terminal elimination phase after single extravascular dosing (Vz/F)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): CL/F
Apparent total systemic clearance after extravascular dosing (CL/F)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Rac(AUC)
Accumulation index area under the concentration-time curve (Rac(AUC))
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): PTR
Peak trough ratio (PTR)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (urine): Aetau
Cumulative amount of study drug excreted into urine from the time of dosing to the start of the next dosing interval (Aetau)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (urine): Aetau%
Percentage of study drug dose excreted into urine from the time of dosing to the start of the next dosing interval (Aetau%)
Measured: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (urine): CLR
Renal clearance (CLR)
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start28 Mar 2016
- Primary completion8 Jun 2017
- Study completion8 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 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, Clinical Pharmacology and Exploratory Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02720263
- Sponsor's protocol ID
- 4345-CL-0002
- Status last verified
- Oct 2024
- First submitted
- 22 Mar 2016
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- 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, Maruff P, Light GA, Uz T, Marek GJ, Zhu T. Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D1 receptor positive allosteric modulator in patients with schizophrenia. Neuropsychopharmacology. 2021 May;46(6):1145-1151. doi: 10.1038/s41386-020-00908-0. Epub 2020 Nov 17.
PubMed 33203954
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 Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP4345 in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT02720263
- Acronym / sponsor ID
- 4345-CL-0002
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, ASP4345
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Mar 2016 (actual)
- Primary completion
- 8 Jun 2017 (actual)
- Study completion
- 8 Jun 2017 (actual)
- First posted
- 25 Mar 2016 (estimated)
- 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 purpose of this study is to evaluate the safety and tolerability of multiple ascending oral doses of ASP4345 in patients with schizophrenia. In addition, this study will evaluate the pharmacokinetics of multiple ascending oral doses of ASP4345 in patients with schizophrenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Double-Blind ASP4345 Multiple Dose Levels | Experimental | Drug: ASP4345ASP4345 will be administered orally as a single daily dose on days 1 through 14 with water. On days 1, 7, and 14, ASP4345 will be administered under fasting conditions. On days 2-6 and 8-13, ASP4345 will be administered under fed conditions. |
| Double-Blind Placebo Multiple Dose | Placebo comparator | Drug: Matching PlaceboMatching placebo capsules will be administered orally as a single daily dose on days 1 through 14 with water. On days 1, 7, and 14, matching placebo capsules will be administered with food. On days 2-6 and 8-13, matching placebo will be administered under fed conditions. |
| Open-Label ASP4345 | Experimental | Drug: ASP4345ASP4345 will be administered orally as a single daily dose on days 1 through 14 with water. On days 1, 7, and 14, ASP4345 will be administered with food. On days 2-6 and 8-13, ASP4345 will be administered under fed conditions. This is an optional cohort where subjects will be enrolled to further characterize pharmacodynamics in the event a higher sample size is necessary to determine changes in electrophysiological biomarkers. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- Patient has a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria.
- A patient is considered operationally stable if the patient has a low to moderate positive symptoms score and moderate negative symptom score on the Positive and Negative Syndrome Scale (PANSS): No more than moderate rating on more than 2 PANSS items P1, P2, P3, P5, P6 (positive symptom section); No more than moderate severity rating for the negative items, N1, N2, N3, N4, N5, N6, N7 (negative symptom section); total PANSS score no more than 80.
- Patient must be in ongoing maintenance antipsychotic therapy other than clozapine (oral or depot), on a stable (≤ 25% change in dose) medication treatment regimen (approved oral or depot formulations of risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone) for ≥ 2 months for oral formulations or ≥ 3 months for depot formulations prior to screening, including concomitant psychotropic medications, such as, trazodone and zolpidem for sleep.
- Patient has a body mass index (BMI) range of 18.5 to 40.0 kg/m2, inclusive, and weighs at least 50 kg at screening.
- Female patient must be of nonchildbearing potential:
Key exclusion criteria (34 listed)
- Female patient who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
- Patient has a known or suspected hypersensitivity to ASP4345 or any components of the formulation used.
- Patient has had previous exposure with ASP4345.
- Patient 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 at screening or at admission to the clinical unit (day 2) will be excluded.
- Patient 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 > than 1.5 times above the ULN at screening or at admission to the clinical unit (day 2). In such a case, the assessment may be repeated once.
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 |
|---|---|---|
| ASP4345Oral | Drug | Double-Blind ASP4345 Multiple Dose Levels, Open-Label ASP4345 |
| Matching PlaceboOral | Drug | Double-Blind Placebo Multiple Dose |
Primary outcome
Safety and tolerability assessed as nature, frequency and severity of adverse events
Time frame: Up to Day 21
Change from baseline in supine blood pressure as a measure of safety and tolerability
Time frame: Baseline and Day 21
Change from baseline in pulse as a measure of safety and tolerability
Time frame: Baseline and Day 21
Change from baseline in oral body temperature as a measure of safety and tolerability
Time frame: Baseline and Day 21
Safety and tolerability assessed by an orthostatic challenge test
Time frame: Up to Day 14
Incidence of positive orthostatic challenge tests will be summarized.
Number of participants with abnormal laboratory values and/or adverse events related to treatment
Time frame: Up to Day 21
Clinical laboratory tests include hematology, biochemistry and urinalysis.
Safety and tolerability assessed by routine 12-lead electrocardiogram (ECG)
Time frame: Up to Day 18
The overall interpretation of 12-lead electrocardiogram (ECG) results (normal, abnormal not clinically significant and abnormal clinically significant) will be summarized.
Safety and tolerability assessed by continuous 12-lead ECG recording
Time frame: Up to Day 14
ECGs will be collected using a 12-lead ECG continuous monitoring system which records continuous digital data.
Safety and tolerability assessed by abuse liability using an Addiction Research Center Inventory (ARCI-49)
Time frame: Up to Day 17
ARCI-49 is a 49-item short form standardized questionnaire for abuse potential liability.
Safety and tolerability assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Up to Day 18
The C-SSRS is a scale that assesses the full spectrum of suicidality: suicidal ideation, intensity of ideation, suicidal behaviors and actual attempts.
Safety and tolerability assessed by Bond-Lader Visual Analog Scale (VAS)
Time frame: Up to Day 17
The VAS will be used to rate patients' feelings in terms of 16 dimensions. The dimensions will be presented as 100 mm lines, the 2 extremes of the emotion (i.e., alert - drowsy) written at each end.
Safety and tolerability assessed by metabolic syndrome: weight circumference
Time frame: Up to Day 14
Safety and tolerability assessed by metabolic syndrome: cholesterol
Time frame: Up to Day 21
Safety and tolerability assessed by metabolic syndrome: triglycerides
Time frame: Up to Day 21
Safety and tolerability assessed by metabolic syndrome: glucose level
Time frame: Up to Day 21
Safety and tolerability assessed by weight
Time frame: Up to Day 14
Safety and tolerability assessed by movement disorder: Abnormal Involuntary Movement Scale (AIMS)
Time frame: Up to Day 14
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 by movement disorder: Simpson Angus Scale (SAS)
Time frame: Up to Day 14
The SAS is a 10-item scale used to rate adverse neurological effects of antipsychotic medications more broadly. Each item is rated from 0 to 4 and a total score will be obtained.
Safety and tolerability assessed by movement disorder: Barnes Akathisia Rating Scale (BARS)
Time frame: Up to Day 14
The BARS is a rating scale used to assess the severity of drug-induced akathisia.
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): tlag
Time frame: Day 1
Time prior to the time corresponding to the first measurable (nonzero) concentration (tlag)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): tmax
Time frame: Day 1 and Day 14
Time of maximum concentration (tmax)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Cmax
Time frame: Day 1 and Day 14
Maximum concentration (Cmax)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): AUCtau
Time frame: Day 1 and Day 14
Area under the concentration-time curve from the time of dosing to the start of the next dosing interval (AUCtau)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Ctrough
Time frame: Days 2 through 14
Concentration immediately prior to dosing at multiple dosing (Ctrough)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): t1/2
Time frame: Day 14
Terminal elimination half-life (t1/2)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): MRTinf
Time frame: Day 14
Mean residence time extrapolated to time infinity (MRTinf)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): terminal elimination rate constant
Time frame: Day 14
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Vz/F
Time frame: Day 14
Apparent volume of distribution during the terminal elimination phase after single extravascular dosing (Vz/F)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): CL/F
Time frame: Day 14
Apparent total systemic clearance after extravascular dosing (CL/F)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): Rac(AUC)
Time frame: Day 14
Accumulation index area under the concentration-time curve (Rac(AUC))
Pharmacokinetics of ASP4345 and its metabolites, if necessary (plasma): PTR
Time frame: Day 14
Peak trough ratio (PTR)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (urine): Aetau
Time frame: Day 14
Cumulative amount of study drug excreted into urine from the time of dosing to the start of the next dosing interval (Aetau)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (urine): Aetau%
Time frame: Day 14
Percentage of study drug dose excreted into urine from the time of dosing to the start of the next dosing interval (Aetau%)
Pharmacokinetics of ASP4345 and its metabolites, if necessary (urine): CLR
Time frame: Day 14
Renal clearance (CLR)
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.
- Derived from this study: PubMed 33203954Desai A, Benner L, Wu R, Gertsik L, Maruff P, Light GA, Uz T, Marek GJ, Zhu T. Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D1 receptor positive allosteric modulator in patients with schizophrenia. Neuropsychopharmacology. 2021 May;46(6):1145-1151. doi: 10.1038/s41386-020-00908-0. Epub 2020 Nov 17.
- 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
Clinical Pharmacology and Exploratory Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASP4345 in people with Schizophrenia, run by Astellas Pharma Global Development, Inc. at 1 site 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 21 inclusion and 34 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 1 site 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 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 as nature, frequency and severity of adverse events (time frame: Up to Day 21). The study lists 34 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 NCT02720263, 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 31 Oct 2024.