Negative Symptoms in Schizophrenia
Conditions
Brief summary
The goal of this clinical trial is to evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of the Co-Administration of Roluperidone and Olanzapine in Adult Subjects with Moderate to Severe Negative Symptoms of Schizophrenia. The main question this clinical trial aims to answer are the pharmacodynamic and pharmacokinetic effects and safety of the concomitant therapy of Roluperidone with an established and widely used antipsychotic, such as olanzapine in order to provide further guidance to clinical practitioners that may prescribe off-label use of these drugs concomitantly in clinical practice. Eligible Participants will undergo the following study phases in the clinic: * Screening Phase: Between 2 and up to 28 days during which study eligibility will be established and subjects receiving psychotropics will be washed out. Subjects will remain inpatient at the clinical site at least through the end of Treatment Phase 2. * Treatment Phase 1: After the Baseline Visit, Roluperidone 64 mg/day will be administered as a monotherapy for 7 days (Days 1-7). * Treatment Phase 2: Concomitant administration of Olanzapine 10 mg/day and Roluperidone 64 mg/day for 10 days, starting on Day 8 (Days 8-17). Subjects may be discharged from the clinic at least 48 hours after the last administration of the study drugs and after the collection of the last plasma sample; however, the inpatient period may be extended at the discretion of the investigator. End of Study (EOS): Will take place at least 14 days after the last dose of the study.
Interventions
64 mg/day oral
DRUGOlanzapine 10 MG
10 mg/day oral
Sponsors
Minerva Neurosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Provided informed consent * Body mass index (BMI) \< 35 kg/m2 * Meets the diagnostic criteria for schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview (MINI) * Documented diagnosis of schizophrenia for at least 1 year before screening * Stable in terms of both positive and negative symptoms of schizophrenia over the last 3 months * Score of \> 20 on the PANSS original negative symptoms subscale (Sum of N1+N2+N3+N4+N5+N6+N7) at Screening and Baseline (Day -1) AND \< 4 points absolute difference between the 2 visits * Discontinued psychotropic medications without risk to their clinical status or safety by Baseline * Female subject, if not of childbearing potential, must be a woman who is post-menopausal or permanently sterilized * Female subject, if of childbearing potential, must test negative for pregnancy and must be using a double barrier contraceptive method * Must be normal metabolizer for P450 CYP 2D6, defined as a subject that has at least one functional allele (eg, \*1, \*2 or \*35), as determined by study-specific genotyping test before the first drug dose is administered * Has a caregiver or family member or health care personnel who can provide information towards assessment and support the subject in terms of compliance with the protocol
Exclusion criteria
* Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14) * PANSS item score of \> 4 on: * P4 Excitement/Hyperactivity * P6 Suspiciousness/persecution * P7 Hostility * G8 Uncooperativeness * G14 Poor impulse control * CDSS total score \> 6 * Score of ≥ 2 on any 2 of items 1, 2, or 3, or a score of ≥ 3 on item 4 of the Barnes Akathisia Rating Scale (BARS) * Has had electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), or repetitive trans-cranial magnetic stimulation (r-TMS) within the 6 months prior to the Screening visit or who are scheduled for ECT, VNS, or r-TMS at any time during the study * Positive urine drug screen for drugs of abuse * Currently taking proton pump inhibitors (PPI) * Current systemic infection (eg, Hepatitis B, Hepatitis C, human immunodeficiency virus \[HIV\], tuberculosis) * Requires or may require concomitant treatment with any other medication likely to increase QT interval * Requires medication inhibiting CYP2D6 * Safety laboratory results show one or more of the following: potassium \<3.4 mmol/L, or calcium \<2.07 mmol/L, or magnesium \<0.70 mmol/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement | Overall - Change from Baseline to End of Study (Day 17) | AIMS is a rating scale to measure tardive dyskinesia (TD). For the scoring, the AIMS scale has 14 items. The first 10 items (under categories of Facial and Oral Movements, Extremity Movements, Trunk Movements, and Global Judgements) are rated from 0 (none) to 4 (severe); the remaining 4 items (Dental Status) are rated yes and no and not counted. The analysis is limited to items 1 to 10, with each rated from 0 to 4. The total score is the sum of all 10 items and with values ranging from 0 to 40. Overall change from baseline to End of Study (Day 17) in AIMS was reported for the Safety Set. Higher scores imply worse outcome. |
| Barnes Akathisia Rating Scale (BARS) | Overall - Change from Baseline to End of Study (Day 17) | BARS is a multiple-choice questionnaire that clinicians may use to provide an assessment of akathisia. The clinician or rater is instructed to observe the subject while standing and while sitting, at least 2 minutes each (total of at least 4 minutes in total). There are 4 areas where the subject is to be evaluated, 1 of these is objective, 2 are subjective, and the final is a global assessment. The BARS scale has 3 items that are rated from 0 (absence/no distress) to 3 (most severe). The BARS rating scale is scored by summing the scales for Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness yielding a total score ranging from 0 to 9. The Total score, which has a possible range from 0-9, is reported. Higher scores imply worse outcome. |
| Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS) | Overall - End of Study (Day 17) | C-SSRS is a measure to identify and assess individuals at risk for suicide. Questions are phrased for an interview format but can be completed as a self-report measure if needed. It measures 4 constructs: severity of ideation, intensity of ideation, behavior, and lethality. It includes stem questions, which if endorsed, prompt additional follow-up questions to obtain more information. For the composite endpoint of suicidal ideation or behavior (1-10), the number and percent of subjects in the Overall Safety Set who experience any one of the ten suicidal ideation or behavior events at End of Study (Day 17). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Days 1 through 17 | AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine. |
| Plasma PK Parameter for Olanzapine Cmax | Treatment Phase 2 (Day 8 through Day 17) | Cmax of olanzapine administered concomitantly with roluperidone |
| Plasma PK Parameter for Olanzapine Tmax | Treatment Phase 2 (Day 8 through Day 17) | Tmax of olanzapine administered concomitantly with roluperidone |
| Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Days 1 through 17 | Cmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine. |
| Plasma PK Parameter for Olanzapine AUC Inf | Treatment Phase 2 (Day 8 through Day 17) | AUC inf olanzapine administered concomitantly with roluperidone |
| Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax) | Days 1 through 17 | Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for Cmax. The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite. |
| Pharmacokinetic Evaluation of Co-administration - AUC 0-24 | Days 1 through 17 | Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for AUC 0-24. The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite. |
| Plasma PK Parameter for Olanzapine AUC 0-24 | Treatment Phase 2 (Day 8 through Day 17) | AUC 0-24 olanzapine administered concomitantly with roluperidone |
| Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Days 1 through 17 | Tmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine. |
| Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Days 1 through 17 | AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine. |
Countries
United States
Participant flow
Pre-assignment details
Participants underwent three study phases: Screening, Treatment Phase 1 and Treatment Phase 2.
Participants by arm
| Arm | Count |
|---|---|
| Overall Safety Set 17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Overall Safety Set |
|---|---|
| Age, Continuous | 36.3 Years STANDARD_DEVIATION 8.2 |
| Body Mass Index at Baseline | 27.3 kg/m2 STANDARD_DEVIATION 4.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 5 / 17 | 5 / 15 |
| serious Total, serious adverse events | 1 / 17 | 0 / 15 |
Outcome results
Primary
Barnes Akathisia Rating Scale (BARS)
BARS is a multiple-choice questionnaire that clinicians may use to provide an assessment of akathisia. The clinician or rater is instructed to observe the subject while standing and while sitting, at least 2 minutes each (total of at least 4 minutes in total). There are 4 areas where the subject is to be evaluated, 1 of these is objective, 2 are subjective, and the final is a global assessment. The BARS scale has 3 items that are rated from 0 (absence/no distress) to 3 (most severe). The BARS rating scale is scored by summing the scales for Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness yielding a total score ranging from 0 to 9. The Total score, which has a possible range from 0-9, is reported. Higher scores imply worse outcome.
Time frame: Overall - Change from Baseline to End of Study (Day 17)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Safety Set | Barnes Akathisia Rating Scale (BARS) | 0.0 score on a scale | Standard Deviation 0 |
Primary
Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement
AIMS is a rating scale to measure tardive dyskinesia (TD). For the scoring, the AIMS scale has 14 items. The first 10 items (under categories of Facial and Oral Movements, Extremity Movements, Trunk Movements, and Global Judgements) are rated from 0 (none) to 4 (severe); the remaining 4 items (Dental Status) are rated yes and no and not counted. The analysis is limited to items 1 to 10, with each rated from 0 to 4. The total score is the sum of all 10 items and with values ranging from 0 to 40. Overall change from baseline to End of Study (Day 17) in AIMS was reported for the Safety Set. Higher scores imply worse outcome.
Time frame: Overall - Change from Baseline to End of Study (Day 17)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Safety Set | Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement | 0.0 score on a scale | Standard Deviation 0 |
Primary
Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS)
C-SSRS is a measure to identify and assess individuals at risk for suicide. Questions are phrased for an interview format but can be completed as a self-report measure if needed. It measures 4 constructs: severity of ideation, intensity of ideation, behavior, and lethality. It includes stem questions, which if endorsed, prompt additional follow-up questions to obtain more information. For the composite endpoint of suicidal ideation or behavior (1-10), the number and percent of subjects in the Overall Safety Set who experience any one of the ten suicidal ideation or behavior events at End of Study (Day 17).
Time frame: Overall - End of Study (Day 17)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Safety Set | Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS) | 0 Participants |
Secondary
Pharmacokinetic Evaluation of Co-administration - AUC 0-24
Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for AUC 0-24. The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite.
Time frame: Days 1 through 17
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Safety Set | Pharmacokinetic Evaluation of Co-administration - AUC 0-24 | Roluperidone Analyte | 451 hr*ng/ml | Geometric Coefficient of Variation 50.5 |
| Overall Safety Set | Pharmacokinetic Evaluation of Co-administration - AUC 0-24 | BFB-520 Analyte | 95.7 hr*ng/ml | Geometric Coefficient of Variation 103.1 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Co-administration - AUC 0-24 | Roluperidone Analyte | 656 hr*ng/ml | Geometric Coefficient of Variation 48.37 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Co-administration - AUC 0-24 | BFB-520 Analyte | 135 hr*ng/ml | Geometric Coefficient of Variation 107.95 |
Secondary
Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax)
Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for Cmax. The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite.
Time frame: Days 1 through 17
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Safety Set | Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax) | Roluperidone Analyte | 39.8 ng/ml | Geometric Coefficient of Variation 46.37 |
| Overall Safety Set | Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax) | BFB-520 Analyte | 5.96 ng/ml | Geometric Coefficient of Variation 89.12 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax) | Roluperidone Analyte | 62.2 ng/ml | Geometric Coefficient of Variation 44.78 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax) | BFB-520 Analyte | 8.54 ng/ml | Geometric Coefficient of Variation 100.1 |
Secondary
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24)
AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Time frame: Days 1 through 17
Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Treatment Phase 1 - Day 1 | 391 hr*ng/mL | Standard Deviation 252 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Treatment Phase 1 - Day 7 | 507 hr*ng/mL | Standard Deviation 278 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Treatment Phase 2 - Day 17 | 720 hr*ng/mL | Standard Deviation 321 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Treatment Phase 1 - Day 1 | 52.3 hr*ng/mL | Standard Deviation 63 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Treatment Phase 1 - Day 7 | 135 hr*ng/mL | Standard Deviation 122 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24) | Treatment Phase 2 - Day 17 | 203 hr*ng/mL | Standard Deviation 225 |
Secondary
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf)
AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Time frame: Days 1 through 17
Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Treatment Phase 1 - Day 1 | 338 hr*ng/mL | Standard Deviation 289 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Treatment Phase 1 - Day 7 | 495 hr*ng/mL | Standard Deviation 272 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Treatment Phase 2 - Day 17 | 883 hr*ng/mL | Standard Deviation 420 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Treatment Phase 1 - Day 1 | 60.7 hr*ng/mL | Standard Deviation 82 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Treatment Phase 1 - Day 7 | 168 hr*ng/mL | Standard Deviation 234 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf) | Treatment Phase 2 - Day 17 | 263 hr*ng/mL | Standard Deviation 280 |
Secondary
Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax)
Cmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Time frame: Days 1 through 17
Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Treatment Phase 1 - Day 1 | 32.5 ng/ml | Standard Deviation 13.7 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Treatment Phase 1 - Day 7 | 43.6 ng/ml | Standard Deviation 19.9 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Treatment Phase 2 - Day 17 | 67.7 ng/ml | Standard Deviation 28.6 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Treatment Phase 1 - Day 1 | 5.00 ng/ml | Standard Deviation 5.69 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Treatment Phase 1 - Day 7 | 7.98 ng/ml | Standard Deviation 6.78 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax) | Treatment Phase 2 - Day 17 | 12.2 ng/ml | Standard Deviation 12.9 |
Secondary
Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax)
Tmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Time frame: Days 1 through 17
Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Treatment Phase 1 - Day 1 | 9.74 hr | Standard Deviation 7.37 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Treatment Phase 1 - Day 7 | 7.47 hr | Standard Deviation 5.73 |
| Overall Safety Set | Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Treatment Phase 2 - Day 17 | 6.20 hr | Standard Deviation 4.56 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Treatment Phase 1 - Day 1 | 16.2 hr | Standard Deviation 6.72 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Treatment Phase 1 - Day 7 | 9.60 hr | Standard Deviation 6.02 |
| Overall Safety Set - Metabolite BFB-520 | Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax) | Treatment Phase 2 - Day 17 | 8.76 hr | Standard Deviation 4.9 |
Secondary
Plasma PK Parameter for Olanzapine AUC 0-24
AUC 0-24 olanzapine administered concomitantly with roluperidone
Time frame: Treatment Phase 2 (Day 8 through Day 17)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Safety Set | Plasma PK Parameter for Olanzapine AUC 0-24 | 587 hr*ng/ml | Standard Deviation 220 |
Secondary
Plasma PK Parameter for Olanzapine AUC Inf
AUC inf olanzapine administered concomitantly with roluperidone
Time frame: Treatment Phase 2 (Day 8 through Day 17)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Safety Set | Plasma PK Parameter for Olanzapine AUC Inf | 719 hr*ng/ml | Standard Deviation 144 |
Secondary
Plasma PK Parameter for Olanzapine Cmax
Cmax of olanzapine administered concomitantly with roluperidone
Time frame: Treatment Phase 2 (Day 8 through Day 17)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Safety Set | Plasma PK Parameter for Olanzapine Cmax | 35.6 ng/ml | Standard Deviation 12.7 |
Secondary
Plasma PK Parameter for Olanzapine Tmax
Tmax of olanzapine administered concomitantly with roluperidone
Time frame: Treatment Phase 2 (Day 8 through Day 17)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Safety Set | Plasma PK Parameter for Olanzapine Tmax | 4.11 hr | Standard Deviation 2.24 |