Bipolar DisorderPhase 1NCT03872596
Trial to Assess the Bioavailability of Quetiapine Versus Seroquel® in Subjects With Schizophrenia or Bipolar Disorder
A Phase 1 study testing Seroquel IR 300mg, Seroquel IR 25mg and Quetiapine Formulation A 300mg in people with Bipolar Disorder and Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial summary
This is a two-part trial. The primary objective of Part A is to estimate the ratio of geometric means of pharmacokinetic (PK) parameters and their within-subject variability for the 300mg quetiapine tablet formulation A and the 300mg quetiapine tablet formulation B compared to 300mg Seroquel. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Bipolar Disorder, Schizophrenia
- What is being tested?
- Seroquel IR 300mg, Seroquel IR 25mg and Quetiapine Formulation A 300mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Mar 2019to 27 Nov 2019
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Part A:
- Must have a current diagnosis of schizophrenia or bipolar disorder, as determined by the Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5) criteria.
- Must have a Body Mass Index between 18 and 35 kg/m^2.
- Good physical health as determined by no clinically significant deviation from normal, in the opinion of the investigator, in medical history, clinical laboratory determination, ECGs, or physical examinations.
- Participants must be considered stable, per the investigator's judgment, on one of the following atypical oral antipsychotic medications at an adequate dose (eg, low- to mid-range of the recommended dose range for the treatment of schizophrenia or bipolar disorder, according to the manufacturer labeling) and for an adequate duration (30 days) prior to the administration of IMP: aripiprazole, brexpiprazole, risperidone, olanzapine, quetiapine, ziprasidone, paliperidone, cariprazine, lurasidone, and asenapine. Other oral antipsychotic medications may be allowed if approved by the medical monitor and sponsor; however, clozapine will not be allowed. Per the investigator's judgment, they should be comfortable with the participant discontinuing background antipsychotic therapy during the trial period and then restarting the antipsychotic therapy once trial participation has been completed.
- Part B:
Show all 11Show fewer
- Male or female participants between 18 and 45 years of age, inclusive.
- Must have a Body Mass Index between 18 and 32 kg/m^2.
- Good physical health as determined by no clinically significant deviation from normal, in the opinion of the investigator, in medical history, clinical laboratory determination, ECGs, or physical examinations.
- Able to provide informed consent prior to the initiation of any protocol-related procedures.
- Male and female participants who are surgically sterile, female participants who have been postmenopausal for at least 12 consecutive months prior to the screening visit, or male participants/female participants (of childbearing potential) who agree to practice 2 of the approved birth control methods from the screening visit and for at least 30 days after the last dose of IMP for a female participant or 80 days after the last dose of IMP for a male participant.
Who cannot join
- Part A:
- Participants who are unable to stop receiving varenicline beyond the screening visit. If a participant is receiving varenicline at the screening visit, attempts should be made to discontinue the medication, if clinically feasible, to allow potential participants to enter the trial.
- Participants 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 (current or over the last 3 months) on the Baseline/Screening Version of the C-SSRS or participants with any suicidal behavior during the 6 months prior to the screening visit.
- Participants currently in an acute relapse of schizophrenia as assessed by the investigator. Bipolar participants who currently have an unstable mood (manic, mixed, or depressed) as assessed by the investigator.
- Participants with a current DSM-5 diagnosis other than schizophrenia or bipolar disorder, including schizoaffective disorder, major depressive disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
- Use of any moderate-strong CYP3A4 inhibitor or inducer within 14 days or 5 plasma half-lives (whichever is longer) prior to the administration of IMP and for the duration of the trial. Weak CYP3A4 inhibitors, including valproic acid, may be allowed based on the investigator's judgment, provided the participant has been on a stable dose for at least 30 days prior to IMP administration and throughout the duration of the trial.
Show all 18Show fewer
- Participants with a history of neuroleptic malignant syndrome, seizure disorder, or clinically significant tardive dyskinesia as assessed by the investigator.
- Subjects with a history of any significant drug allergy or known or suspected hypersensitivity to antipsychotics, in particular to quetiapine.
- Participants who are maintained on long-acting insulin.
- Any participant who does not successfully tolerate a quetiapine dose of 300 mg BID during the titration period of this trial.
- Part B:
- History of any significant drug allergy to quetiapine, prescription drugs, non-prescription drugs, or food.
- Any history of significant bleeding or hemorrhagic tendencies.
- Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to screening through the end of the trial (eg, occupational exposure to pesticides, organic solvents, etc).
- Participants who have supine blood pressure after resting for ≥ 5 minutes, higher than 130/80 mmHg or lower than 100/50 mmHg (systolic/diastolic). The sponsor may allow exceptions if they are not deemed clinically significant.
- Participants who have a supine pulse rate, after resting for ≥ 5 minutes, outside the range of 60 to 90 beats per minute. The sponsor may allow exceptions if they are not deemed clinically significant (eg, bradycardia attributable to superior physical fitness).
- History of serious mental disorders that, in the opinion of the investigator, would exclude the participant from participating in this trial.
- Use of any CYP3A4 inhibitors or CYP3A4 inducers within 14 days or 5 plasma half-lives (whichever is longer) prior to the administration of IMP and for the duration of the trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
Collaborative Neurosciences Network, LLC
Long Beach, California, 90806
About this study
Official title: A Phase 1, 2-Part, Open-Label, Randomized, Crossover Pilot Trial to Assess the Relative Bioavailability of Quetiapine Versus Seroquel® 300-mg Oral Tablets in Subjects With Schizophrenia or Bipolar Disorder and 25-mg Oral Tablets in Healthy Subjects
This is a two-part trial.
The primary objective of Part A is to estimate the ratio of geometric means of pharmacokinetic (PK) parameters and their within-subject variability for the 300mg quetiapine tablet formulation A and the 300mg quetiapine tablet formulation B compared to 300mg Seroquel.
The primary objective of Part B is to estimate the ratio of geometric means of PK parameters and their within-subject variability for the selected tablet formulation from Part A of 25mg quetiapine compared to 25mg Seroquel.
- Conditions
- Bipolar Disorder, Schizophrenia
- Being tested
- Seroquel IR 300mg, Seroquel IR 25mg, Quetiapine Formulation A 300mg, Quetiapine Formulation B 300mg, Quetiapine Formulation 25mg
- Keywords
- Seroquel, Digital Medicine Quetiapine, Pharmacokinetics, Bioavailability
- Medical subject headings
- Bipolar Disorder, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Seroquel IR 300mgDrug
Administered during Part A, administered orally BID with water, over 5 days.
Seroquel IR 25mgDrug
Administered during Part B, as a single, 25mg dose taken with water.
Quetiapine Formulation A 300mgDrug
Administered during Part A, administered orally BID with water, over 5 days.
Quetiapine Formulation B 300mgDrug
Administered during Part A, administered orally BID with water, over 5 days.
Quetiapine Formulation 25mgDrug
Administered during Part B, as a single, 25mg dose taken with water.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Sequence 1 | Experimental | Titration Period:
All participants will complete the titration period to establish tolerability. Depending on exposure prior to the trial, participants will titrate up to and including a dose of 300mg twice a day (BID) prior to randomization.
Treatment Period:
Participants will receive Seroquel IR (tablet, orally, 300mg, BID) on Days 1-5, Quetiapine Formulation A (tablet, orally, 300mg, BID) on Days 6-10 and Quetiapine Formulation B (tablet, orally, 300mg, BID) on Days 11-15. Receives: Drug: Seroquel IR 300mg; Drug: Quetiapine Formulation A 300mg; Drug: Quetiapine Formulation B 300mg |
| Part A: Sequence 2 | Experimental | Titration Period:
All participants will complete the titration period to establish tolerability. Depending on exposure prior to the trial, participants will titrate up to and including a dose of 300mg BID prior to randomization.
Treatment Period:
Participants will receive Quetiapine Formulation A (tablet, orally, 300mg, BID) on Days 1-5, Quetiapine Formulation B (tablet, orally, 300mg, BID) on Days 6-10 and Seroquel IR (tablet, orally, 300mg, BID) on Days 11-15. Receives: Drug: Seroquel IR 300mg; Drug: Quetiapine Formulation A 300mg; Drug: Quetiapine Formulation B 300mg |
| Part A: Sequence 3 | Experimental | Titration Period:
All participants will complete the titration period to establish tolerability. Depending on exposure prior to the trial, participants will titrate up to and including a dose of 300mg BID prior to randomization.
Treatment Period:
Participants will receive Quetiapine Formulation B (tablet, orally, 300mg, BID) on Days 1-5, Seroquel IR (tablet, orally, 300mg, BID) on Days 6-10 and Quetiapine Formulation A (tablet, orally, 300mg, BID) on Days 11-15. Receives: Drug: Seroquel IR 300mg; Drug: Quetiapine Formulation A 300mg; Drug: Quetiapine Formulation B 300mg |
| Part B: Sequence 1 | Experimental | Participants will receive Seroquel IR (tablet, orally, 25mg) on Day 1 and Quetiapine formulation established in Part A (tablet, orally, 25mg) on Day 4. Receives: Drug: Seroquel IR 25mg; Drug: Quetiapine Formulation 25mg |
| Part B: Sequence 2 | Experimental | Participants will receive Quetiapine formulation established in Part A (tablet, orally, 25mg) on Day 1 and Seroquel IR (tablet, orally, 25mg) on Day 4. Receives: Drug: Seroquel IR 25mg; Drug: Quetiapine Formulation 25mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Maximum Observed Plasma Concentration (Cmax) for Quetiapine
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Measured: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Area Under the Concentration-Time Curve Calculated to the Last Observable Concentration at Time t (AUCt) for Quetiapine
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Measured: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part B: Maximum Observed Plasma Concentration (Cmax) for Quetiapine
Measured: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Area Under the Concentration-Time Curve Calculated to the Last Observable Concentration at Time t (AUCt) for Quetiapine
Measured: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC∞) for Quetiapine
Measured: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Secondary outcomes (16)
Part A: Time to Maximum (Peak) Plasma Concentration (tmax) for Quetiapine
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Measured: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Terminal-Phase Elimination Half-Life (t1/2,z) for Quetiapine
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Measured: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Apparent Clearance of Drug from Plasma After Extravascular Administration (CL/F) for Quetiapine
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Measured: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Percentage of Participants who Experience at Least One Treatment-Emergent Adverse Event
An adverse event is defined as as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A Treatment-Emergent Adverse Event (TEAE) is defined as an adverse event that occurs after treatment has begun.
Measured: Day 1 to End of Follow-Up (Day 45[+/- 2 days])
Part A: Percentage of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs
Vital signs will include blood pressure, heart rate, temperature, and respiratory rate.
Measured: Baseline (Day -1) to Day 11
Part A: Percentage of Participants who Experience a Significant Change from Baseline in ECGs
Standard 12-lead electrocardiograms will be used.
Measured: Baseline (Day -1) to Day 11
Part A: Percentage of Participants who Experience a Significant Change from Baseline in Clinical Laboratory Tests
Clinical laboratory tests will be conducted at scheduled time points during Part A and Part B, including hematology, urinalysis, serum chemistry, drug screen and additional tests.
Measured: Baseline (Day -1) to Day 15
Part A: Change from Baseline in Columbia-Suicide Severity Rating Scale Score
Suicidality will be monitored throughout the trial using the C-SSRS (Columbia-Suicide Severity Rating Scale). This scale consists of a baseline evaluation that assesses the lifetime experience of the subject with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last assessment.The Baseline/ Screening Version and the Since Last Visit version of the C-SSRS will be completed by trained trial site staff at each visit. A numerical score will correspond to one of ten categories relating to suicidal ideation and suicidal behavior. A higher score indicates a higher risk of suicidal behavior, but an answer of 'yes' to any question indicates some risk.
Measured: Baseline (Day -1) and Day 15
Part B: Time to Maximum (Peak) Plasma Concentration (tmax) for Quetiapine
Measured: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Terminal-Phase Elimination Half-Life (t1/2,z) for Quetiapine
Measured: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Apparent Clearance of Drug from Plasma After Extravascular Administration (CL/F) for Quetiapine
Measured: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Percentage of Participants who Experience at Least One Treatment-Emergent Adverse Event
An adverse event is defined as as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A Treatment-Emergent Adverse Event (TEAE) is defined as an adverse event that occurs after treatment has begun.
Measured: Day 1 to End of Follow-Up (Day 34 [+ 2 Days])
Part B: Percentage of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs
Measured: Baseline (Day -1) to Day 6
Part B: Percentage of Participants who Experience a Significant Change from Baseline in ECGs
Standard 12-lead electrocardiograms will be used.
Measured: Baseline (Day -1) to Day 6
Part B: Percentage of Participants who Experience a Significant Change from Baseline in Clinical Laboratory Tests
Clinical laboratory tests will be conducted at scheduled time points during Part A and Part B, including hematology, urinalysis, serum chemistry, drug screen and additional tests.
Measured: Baseline (Day -1) to Day 6
Part B: Change from Baseline in Columbia-Suicide Severity Rating Scale Score
Suicidality will be monitored throughout the trial using the C-SSRS (Columbia-Suicide Severity Rating Scale). This scale consists of a baseline evaluation that assesses the lifetime experience of the subject with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last assessment.The Baseline/ Screening Version and the Since Last Visit version of the C-SSRS will be completed by trained trial site staff at each visit. A numerical score will correspond to one of ten categories relating to suicidal ideation and suicidal behavior. A higher score indicates a higher risk of suicidal behavior, but an answer of 'yes' to any question indicates some risk.
Measured: Baseline (Day -1) and Day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2019
- Study start27 Mar 2019
- Primary completion30 Oct 2019
- Study completion27 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a two-part, crossover study. In Part A, participants will be randomized into one of three treatment sequences, each receiving Seroquel immediate release (IR) 300mg, Quetiapine Formulation A 300mg and Quetiapine Formulation B 300mg. In Part B, participants will be randomized into one of two treatment sequences, each receiving Seroquel IR 25mg and Quetiapine 25mg, the formulation of which will be established in Part A.
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Ernest Roos, M.D., Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03872596
- Sponsor's protocol ID
- 304-201-00001
- Status last verified
- Jun 2019
- First submitted
- 12 Mar 2019
- Last updated
- 2 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, 2-Part, Open-Label, Randomized, Crossover Pilot Trial to Assess the Relative Bioavailability of Quetiapine Versus Seroquel® 300-mg Oral Tablets in Subjects With Schizophrenia or Bipolar Disorder and 25-mg Oral Tablets in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03872596
- Acronym / sponsor ID
- 304-201-00001
- Conditions
- Bipolar Disorder, Schizophrenia
- Keywords
- Seroquel, Digital Medicine Quetiapine, Pharmacokinetics, Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 27 Mar 2019 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 27 Nov 2019 (actual)
- First posted
- 13 Mar 2019 (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.
This is a two-part trial.
The primary objective of Part A is to estimate the ratio of geometric means of pharmacokinetic (PK) parameters and their within-subject variability for the 300mg quetiapine tablet formulation A and the 300mg quetiapine tablet formulation B compared to 300mg Seroquel.
The primary objective of Part B is to estimate the ratio of geometric means of PK parameters and their within-subject variability for the selected tablet formulation from Part A of 25mg quetiapine compared to 25mg Seroquel.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- This is a two-part, crossover study. In Part A, participants will be randomized into one of three treatment sequences, each receiving Seroquel immediate release (IR) 300mg, Quetiapine Formulation A 300mg and Quetiapine Formulation B 300mg. In Part B, participants will be randomized into one of two treatment sequences, each receiving Seroquel IR 25mg and Quetiapine 25mg, the formulation of which will be established in Part A.
| Arm | Type | Receives |
|---|---|---|
| Part A: Sequence 1 | Experimental | Drug: Seroquel IR 300mg, Drug: Quetiapine Formulation A 300mg, Drug: Quetiapine Formulation B 300mgTitration Period: All participants will complete the titration period to establish tolerability. Depending on exposure prior to the trial, participants will titrate up to and including a dose of 300mg twice a day (BID) prior to randomization. Treatment Period: Participants will receive Seroquel IR (tablet, orally, 300mg, BID) on Days 1-5, Quetiapine Formulation A (tablet, orally, 300mg, BID) on Days 6-10 and Quetiapine Formulation B (tablet, orally, 300mg, BID) on Days 11-15. |
| Part A: Sequence 2 | Experimental | Drug: Seroquel IR 300mg, Drug: Quetiapine Formulation A 300mg, Drug: Quetiapine Formulation B 300mgTitration Period: All participants will complete the titration period to establish tolerability. Depending on exposure prior to the trial, participants will titrate up to and including a dose of 300mg BID prior to randomization. Treatment Period: Participants will receive Quetiapine Formulation A (tablet, orally, 300mg, BID) on Days 1-5, Quetiapine Formulation B (tablet, orally, 300mg, BID) on Days 6-10 and Seroquel IR (tablet, orally, 300mg, BID) on Days 11-15. |
| Part A: Sequence 3 | Experimental | Drug: Seroquel IR 300mg, Drug: Quetiapine Formulation A 300mg, Drug: Quetiapine Formulation B 300mgTitration Period: All participants will complete the titration period to establish tolerability. Depending on exposure prior to the trial, participants will titrate up to and including a dose of 300mg BID prior to randomization. Treatment Period: Participants will receive Quetiapine Formulation B (tablet, orally, 300mg, BID) on Days 1-5, Seroquel IR (tablet, orally, 300mg, BID) on Days 6-10 and Quetiapine Formulation A (tablet, orally, 300mg, BID) on Days 11-15. |
| Part B: Sequence 1 | Experimental | Drug: Seroquel IR 25mg, Drug: Quetiapine Formulation 25mgParticipants will receive Seroquel IR (tablet, orally, 25mg) on Day 1 and Quetiapine formulation established in Part A (tablet, orally, 25mg) on Day 4. |
| Part B: Sequence 2 | Experimental | Drug: Seroquel IR 25mg, Drug: Quetiapine Formulation 25mgParticipants will receive Quetiapine formulation established in Part A (tablet, orally, 25mg) on Day 1 and Seroquel IR (tablet, orally, 25mg) on Day 4. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Must have a current diagnosis of schizophrenia or bipolar disorder, as determined by the Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5) criteria.
- Must have a Body Mass Index between 18 and 35 kg/m^2.
- Good physical health as determined by no clinically significant deviation from normal, in the opinion of the investigator, in medical history, clinical laboratory determination, ECGs, or physical examinations.
- Participants must be considered stable, per the investigator's judgment, on one of the following atypical oral antipsychotic medications at an adequate dose (eg, low- to mid-range of the recommended dose range for the treatment of schizophrenia or bipolar disorder, according to the manufacturer labeling) and for an adequate duration (30 days) prior to the administration of IMP: aripiprazole, brexpiprazole, risperidone, olanzapine, quetiapine, ziprasidone, paliperidone, cariprazine, lurasidone, and asenapine. Other oral antipsychotic medications may be allowed if approved by the medical monitor and sponsor; however, clozapine will not be allowed. Per the investigator's judgment, they should be comfortable with the participant discontinuing background antipsychotic therapy during the trial period and then restarting the antipsychotic therapy once trial participation has been completed.
- Male or female participants between 18 and 45 years of age, inclusive.
Key exclusion criteria (18 listed)
- Participants who are unable to stop receiving varenicline beyond the screening visit. If a participant is receiving varenicline at the screening visit, attempts should be made to discontinue the medication, if clinically feasible, to allow potential participants to enter the trial.
- Participants 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 (current or over the last 3 months) on the Baseline/Screening Version of the C-SSRS or participants with any suicidal behavior during the 6 months prior to the screening visit.
- Participants currently in an acute relapse of schizophrenia as assessed by the investigator. Bipolar participants who currently have an unstable mood (manic, mixed, or depressed) as assessed by the investigator.
- Participants with a current DSM-5 diagnosis other than schizophrenia or bipolar disorder, including schizoaffective disorder, major depressive disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
- Use of any moderate-strong CYP3A4 inhibitor or inducer within 14 days or 5 plasma half-lives (whichever is longer) prior to the administration of IMP and for the duration of the trial. Weak CYP3A4 inhibitors, including valproic acid, may be allowed based on the investigator's judgment, provided the participant has been on a stable dose for at least 30 days prior to IMP administration and throughout the duration of the trial.
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 |
|---|---|---|
| Seroquel IR 300mgAdministered during Part A, administered orally BID with water, over 5 days. | Drug | Part A: Sequence 1, Part A: Sequence 2, Part A: Sequence 3 |
| Seroquel IR 25mgAdministered during Part B, as a single, 25mg dose taken with water. | Drug | Part B: Sequence 1, Part B: Sequence 2 |
| Quetiapine Formulation A 300mgAdministered during Part A, administered orally BID with water, over 5 days. | Drug | Part A: Sequence 1, Part A: Sequence 2, Part A: Sequence 3 |
| Quetiapine Formulation B 300mgAdministered during Part A, administered orally BID with water, over 5 days. | Drug | Part A: Sequence 1, Part A: Sequence 2, Part A: Sequence 3 |
| Quetiapine Formulation 25mgAdministered during Part B, as a single, 25mg dose taken with water. | Drug | Part B: Sequence 1, Part B: Sequence 2 |
Primary outcome
Part A: Maximum Observed Plasma Concentration (Cmax) for Quetiapine
Time frame: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Part A: Area Under the Concentration-Time Curve Calculated to the Last Observable Concentration at Time t (AUCt) for Quetiapine
Time frame: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Pharmacokinetic endpoint analysis will be done separately for formulation A and formulation B.
Part B: Maximum Observed Plasma Concentration (Cmax) for Quetiapine
Time frame: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Area Under the Concentration-Time Curve Calculated to the Last Observable Concentration at Time t (AUCt) for Quetiapine
Time frame: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC∞) for Quetiapine
Time frame: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
16 secondary outcomes
Part A: Time to Maximum (Peak) Plasma Concentration (tmax) for Quetiapine
Time frame: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Terminal-Phase Elimination Half-Life (t1/2,z) for Quetiapine
Time frame: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Apparent Clearance of Drug from Plasma After Extravascular Administration (CL/F) for Quetiapine
Time frame: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15
Part A: Percentage of Participants who Experience at Least One Treatment-Emergent Adverse Event
Time frame: Day 1 to End of Follow-Up (Day 45[+/- 2 days])
Part A: Percentage of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs
Time frame: Baseline (Day -1) to Day 11
Part A: Percentage of Participants who Experience a Significant Change from Baseline in ECGs
Time frame: Baseline (Day -1) to Day 11
Part A: Percentage of Participants who Experience a Significant Change from Baseline in Clinical Laboratory Tests
Time frame: Baseline (Day -1) to Day 15
Part A: Change from Baseline in Columbia-Suicide Severity Rating Scale Score
Time frame: Baseline (Day -1) and Day 15
Part B: Time to Maximum (Peak) Plasma Concentration (tmax) for Quetiapine
Time frame: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Terminal-Phase Elimination Half-Life (t1/2,z) for Quetiapine
Time frame: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Apparent Clearance of Drug from Plasma After Extravascular Administration (CL/F) for Quetiapine
Time frame: Predose (within 30 minutes prior to dosing), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12 (Days 1 to 4), 24, 36 (Days 2 and 5), and 48 (Days 3 and 6) hours post dose
Part B: Percentage of Participants who Experience at Least One Treatment-Emergent Adverse Event
Time frame: Day 1 to End of Follow-Up (Day 34 [+ 2 Days])
Part B: Percentage of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs
Time frame: Baseline (Day -1) to Day 6
Part B: Percentage of Participants who Experience a Significant Change from Baseline in ECGs
Time frame: Baseline (Day -1) to Day 6
Part B: Percentage of Participants who Experience a Significant Change from Baseline in Clinical Laboratory Tests
Time frame: Baseline (Day -1) to Day 6
Part B: Change from Baseline in Columbia-Suicide Severity Rating Scale Score
Time frame: Baseline (Day -1) and Day 6
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 2 Sep 2020.
- Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Related trials for Bipolar Disorder
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)
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.
Ernest Roos, M.D. study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
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 Seroquel IR 300mg, Seroquel IR 25mg and Quetiapine Formulation A 300mg in people with Bipolar Disorder and Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, 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 11 inclusion and 18 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 2 Sep 2020. 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. 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?
Part A: Maximum Observed Plasma Concentration (Cmax) for Quetiapine (time frame: Pre-dose on days 4, 9 and 14, 12 hours post morning dose on Days 4, 9 and 14 and pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 3, 4, 6, 8, 10 and 12 hours post morning dose on days 5, 10 and 15). The study lists 5 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 2 Sep 2020.