SchizophreniaPhase 1NCT02968121
Safety and Tolerability Study of Single-dose Administration of Brexpiprazole in Adult Subjects With Schizophrenia
A Phase 1 study testing Brexpiprazole, OPDC-34712 in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 2 sites in United States.
Trial summary
To determine the pharmacokinetics, safety and tolerability of brexpiprazole administered subcutaneously or intramuscularly in adults with schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Brexpiprazole, OPDC-34712
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2017to 14 Dec 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males and females between 18 and 64 years of age, inclusive, at the screening visit with a diagnosis of schizophrenia as defined by DSM-V criteria.
- Body mass index between 18 and 35 kg/m^2 at the screening visit.
- Good physical health as determined by no clinically significant deviation from normal.
- Ability to provide informed consent and/or consent obtained from a legally acceptable representative (as required by IRB), prior to the initiation of any protocol-required procedures.
- Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to the screening visit, or male subjects/female subjects (of childbearing potential) who agree to remain abstinent or to practice 2 of the approved birth control methods from the screening visit and for at least 150 days after the dose of IMP for a female subject or 180 days after the dose of IMP for a male subject.
Who cannot join
- Subjects who have:
- Met DSM-V criteria for substance use disorder within the past 180 days; including alcohol and benzodiazepines, excluding caffeine/nicotine.
- A positive drug screen for drugs of abuse (excluding stimulants, other prescribed medications, and marijuana [if in investigator's documented opinion the subject does not meet DSM-V criteria for substance use disorder]).
- Use of more than 1 psychotropic medication at the screening or baseline visit, except for oral brexpiprazole administered during the brexpiprazole tolerability testing (if applicable) and current oral antipsychotic medication.
- Use of varenicline beyond screening.
- Subjects who have participated in any clinical trial involving a psychotropic medication within 1 month prior to the administration of IMP or 5 half-lives from last IMP administration whichever is longer.
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- Subjects who have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on questions 4 or 5 on the Baseline Version of the C-SSRS.
- Subjects currently in an acute relapse of schizophrenia as assessed by the investigator.
- Subjects with a current DSM-V diagnosis other than schizophrenia. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Collaborative Neuro Science (CNS)
Garden Grove, California, 92845
CNRI
San Diego, California, 92102
About this study
Official title: A Phase 1, Two-part, Open-label, Randomized, Exploratory and Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Brexpiprazole Long-acting Injectable Administered Subcutaneously or Intramuscularly in Adult Subjects With Schizophrenia
To determine the pharmacokinetics, safety and tolerability of brexpiprazole administered subcutaneously or intramuscularly in adults with schizophrenia.
Read the detailed description
This trial is designed to assess the pharmacokinetics, safety and tolerability of brexpiprazole in the treatment of subjects with schizophrenia. The trial will consist of two parts across 13-36 months. The trial population will include approximately 110 male \& female subjects between 18 and 64 years of age (inclusive) with a diagnosis of schizophrenia as defined by DSM-V criteria.
- Conditions
- Schizophrenia
- Being tested
- Brexpiprazole, OPDC-34712
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brexpiprazole, OPDC-34712Drug
| Study group | Role | What they receive |
|---|---|---|
| Part A: Single Dose Injection: Subcutaneous | Experimental | Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous Receives: Drug: Brexpiprazole, OPDC-34712 |
| Part A: Single Dose Injection: Intramuscular | Experimental | Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous Receives: Drug: Brexpiprazole, OPDC-34712 |
| Part B: Cohort 1 | Experimental | Drug: Brexpiprazole, OPDC-34712 Once, SC or IM Receives: Drug: Brexpiprazole, OPDC-34712 |
| Part B: Cohort 2 | Experimental | Drug: Brexpiprazole, OPDC-34712 Once, SC or IM Receives: Drug: Brexpiprazole, OPDC-34712 |
| Part B: Cohort 3 | Experimental | Drug: Brexpiprazole, OPDC-34712 Once, SC or IM Receives: Drug: Brexpiprazole, OPDC-34712 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Suicidality via Columbia-Suicide Severity Rating Scale
Baseline version and Since Last Visit version of CSSRS will be completed by trained trial center staff
Measured: Part A: Screening to Day 182; Part B: Screening to Day 126
Number of reported Adverse Events (AE)
Measured: Part A: 182 days; Part B: 126 days
Clinical Laboratory Tests
Hematology, serum chemistry, urinalysis, drug screen, etc. will be performed.
Measured: Part A: 182 days; Part B: 126 days
Change in physical exam results
Investigator or designee will perform complete physical exam and document any clinically significant conditions. Body height and weight will also be measured for BMI calculation and weight will be measured as part of all subsequent physical exams.
Measured: Part A: Screening to Day 182; Part B: Screening to Day 126
Change in Systolic/Diastolic blood pressure from screening to end of study
Heart rate and body temperature will also be obtained prior to PK blood draws and ECG.
Measured: Part A: Screening to Day 182; Part B: Screening to Day 126
ECG Reading
12-lead ECG will be collected in triplicate (5 minutes apart). heart rate, ventricular rate, RR interval, PR interval, QRS duration and QT intervals will be recorded. QTcF and corrected QT interval using Bazett's formula will be calculated.
Measured: Part A: 182 days; Part B: 126 days
Extrapyramidal Symptoms (EPS) Rating Scale
SAS, AIMS \& BARS will be assess by trained trial center staff
Measured: Part A: 182 days; Part B: 126 days
Investigator's assessment of injection site
Injection site will be assessed. Injection site will also be inspected for seepage after needle is withdrawn.
Measured: Part A: 182 days; Part B: 126 days
Visual analog scale (VAS) scores for pain reception
Measured: Part A: 182 days; Part B: 126 days
Secondary outcomes (6)
Maximum peak plasma concentration (Cmax) [Pharmacokinetics]
Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded.
PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411.
Measured: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Time of Cmax (tmax) [Pharmacokinetics]
Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded.
PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411
Measured: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Area under the concentration-time curve (AUC) from time zero to time "t" (Last observable concentration; AUCt) [Pharmacokinetics]
Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded.
PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411
Measured: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
AUC from time zero to infinity (AUC∞) [Pharmacokinetics]
Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded.
PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411
Measured: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Terminal-phase elimination half-life (t1/2,z) [Pharmacokinetics]
Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded.
PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411
Measured: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Apparent clearance of drug from plasma after extravascular administration (CL/F; brexpiprazole only) [Pharmacokinetics]
Samples will also be collected on Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112, 126, 154, and 182/ET or until plasma concentrations of brexpiprazole are BLQ, whichever is longer based on monthly PK sampling (samples will be collected between 8 AM and 2 PM on the indicated nondosing day). If a PK blood sample cannot be drawn at the designated time on Day 1, a window of ± 15 minutes for each blood draw is acceptable with the exact time recorded.
PK parameters will be assessed for plasma brexpiprazole and its metabolite(s) including DM-3411
Measured: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2016 (estimated)
- Study startJan 2017
- Primary completion14 Dec 2017
- Study completion14 Dec 2017
Why it stopped: Part A of study was completed per protocol. Conduct of Part B of the study (confirmatory phase) was not necessary.
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 Otsuka Pharmaceutical Development & Commercialization, 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02968121
- Sponsor's protocol ID
- 331-201-00033
- Status last verified
- Jan 2018
- First submitted
- 2 Nov 2016
- Last updated
- 12 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Two-part, Open-label, Randomized, Exploratory and Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Brexpiprazole Long-acting Injectable Administered Subcutaneously or Intramuscularly in Adult Subjects With Schizophrenia
- ClinicalTrials.gov ID
- NCT02968121
- Acronym / sponsor ID
- 331-201-00033
- Conditions
- Schizophrenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Part A of study was completed per protocol. Conduct of Part B of the study (confirmatory phase) was not necessary.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Study start
- Jan 2017 (actual)
- Primary completion
- 14 Dec 2017 (actual)
- Study completion
- 14 Dec 2017 (actual)
- First posted
- 18 Nov 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.
To determine the pharmacokinetics, safety and tolerability of brexpiprazole administered subcutaneously or intramuscularly in adults with schizophrenia.
Detailed description
This trial is designed to assess the pharmacokinetics, safety and tolerability of brexpiprazole in the treatment of subjects with schizophrenia. The trial will consist of two parts across 13-36 months. The trial population will include approximately 110 male \& female subjects between 18 and 64 years of age (inclusive) with a diagnosis of schizophrenia as defined by DSM-V criteria.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: Single Dose Injection: Subcutaneous | Experimental | Drug: Brexpiprazole, OPDC-34712Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous |
| Part A: Single Dose Injection: Intramuscular | Experimental | Drug: Brexpiprazole, OPDC-34712Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous |
| Part B: Cohort 1 | Experimental | Drug: Brexpiprazole, OPDC-34712Drug: Brexpiprazole, OPDC-34712 Once, SC or IM |
| Part B: Cohort 2 | Experimental | Drug: Brexpiprazole, OPDC-34712Drug: Brexpiprazole, OPDC-34712 Once, SC or IM |
| Part B: Cohort 3 | Experimental | Drug: Brexpiprazole, OPDC-34712Drug: Brexpiprazole, OPDC-34712 Once, SC or IM |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Males and females between 18 and 64 years of age, inclusive, at the screening visit with a diagnosis of schizophrenia as defined by DSM-V criteria.
- Body mass index between 18 and 35 kg/m^2 at the screening visit.
- Good physical health as determined by no clinically significant deviation from normal.
- Ability to provide informed consent and/or consent obtained from a legally acceptable representative (as required by IRB), prior to the initiation of any protocol-required procedures.
- Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to the screening visit, or male subjects/female subjects (of childbearing potential) who agree to remain abstinent or to practice 2 of the approved birth control methods from the screening visit and for at least 150 days after the dose of IMP for a female subject or 180 days after the dose of IMP for a male subject.
Key exclusion criteria (9 listed)
- Subjects who have:
- Met DSM-V criteria for substance use disorder within the past 180 days; including alcohol and benzodiazepines, excluding caffeine/nicotine.
- A positive drug screen for drugs of abuse (excluding stimulants, other prescribed medications, and marijuana [if in investigator's documented opinion the subject does not meet DSM-V criteria for substance use disorder]).
- Use of more than 1 psychotropic medication at the screening or baseline visit, except for oral brexpiprazole administered during the brexpiprazole tolerability testing (if applicable) and current oral antipsychotic medication.
- Use of varenicline beyond screening.
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 |
|---|---|---|
| Brexpiprazole, OPDC-34712 | Drug | Part A: Single Dose Injection: Intramuscular, Part A: Single Dose Injection: Subcutaneous, Part B: Cohort 1, Part B: Cohort 2, Part B: Cohort 3 |
Primary outcome
Change in Suicidality via Columbia-Suicide Severity Rating Scale
Time frame: Part A: Screening to Day 182; Part B: Screening to Day 126
Baseline version and Since Last Visit version of CSSRS will be completed by trained trial center staff
Number of reported Adverse Events (AE)
Time frame: Part A: 182 days; Part B: 126 days
Clinical Laboratory Tests
Time frame: Part A: 182 days; Part B: 126 days
Hematology, serum chemistry, urinalysis, drug screen, etc. will be performed.
Change in physical exam results
Time frame: Part A: Screening to Day 182; Part B: Screening to Day 126
Investigator or designee will perform complete physical exam and document any clinically significant conditions. Body height and weight will also be measured for BMI calculation and weight will be measured as part of all subsequent physical exams.
Change in Systolic/Diastolic blood pressure from screening to end of study
Time frame: Part A: Screening to Day 182; Part B: Screening to Day 126
Heart rate and body temperature will also be obtained prior to PK blood draws and ECG.
ECG Reading
Time frame: Part A: 182 days; Part B: 126 days
12-lead ECG will be collected in triplicate (5 minutes apart). heart rate, ventricular rate, RR interval, PR interval, QRS duration and QT intervals will be recorded. QTcF and corrected QT interval using Bazett's formula will be calculated.
Extrapyramidal Symptoms (EPS) Rating Scale
Time frame: Part A: 182 days; Part B: 126 days
SAS, AIMS \& BARS will be assess by trained trial center staff
Investigator's assessment of injection site
Time frame: Part A: 182 days; Part B: 126 days
Injection site will be assessed. Injection site will also be inspected for seepage after needle is withdrawn.
Visual analog scale (VAS) scores for pain reception
Time frame: Part A: 182 days; Part B: 126 days
6 secondary outcomes
Maximum peak plasma concentration (Cmax) [Pharmacokinetics]
Time frame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Time of Cmax (tmax) [Pharmacokinetics]
Time frame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Area under the concentration-time curve (AUC) from time zero to time "t" (Last observable concentration; AUCt) [Pharmacokinetics]
Time frame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
AUC from time zero to infinity (AUC∞) [Pharmacokinetics]
Time frame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Terminal-phase elimination half-life (t1/2,z) [Pharmacokinetics]
Time frame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Apparent clearance of drug from plasma after extravascular administration (CL/F; brexpiprazole only) [Pharmacokinetics]
Time frame: Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose)
Results and safety
The study was stopped early (reason given: Part A of study was completed per protocol. Conduct of Part B of the study (confirmatory phase) was not necessary.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2018.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Brexpiprazole, OPDC-34712 in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, 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 5 inclusion and 9 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: stopped early, as of the sponsor's last update on 12 Jan 2018. 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 was stopped early (reason given: Part A of study was completed per protocol. Conduct of Part B of the study (confirmatory phase) was not necessary.). Results are not available in the source record.
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 in Suicidality via Columbia-Suicide Severity Rating Scale (time frame: Part A: Screening to Day 182; Part B: Screening to Day 126). The study lists 9 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 12 Jan 2018.