Psychiatric Disorders, Schizophrenia
Conditions
Keywords
Schizophrenia, psychiatric disorders, renal failure
Brief summary
This trial is an open-label, multi-center, parallel-arm, single-dose trial in 2 groups: 1 group of subjects with normal renal function and 1 group of severely renally impaired subjects.
Interventions
DRUGOPC-34712
administered orally
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female (non-childbearing potential) subjects ≥ 18 years of age. * Ability to provide written informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial. * Male and female subjects who are surgically sterile; female subjects who have been postmenopausal for at least 12 consecutive months (confirmed by follicle stimulating hormone sample at Screening); or male subjects who agree to remain abstinent or to practice double-barrier forms of birth control and refrain from sperm donation from trial Screening through 90 days from the last dose of the investigational medicinal product. * Body weight within ± 35% of ideal body weight as defined in the 1983 Metropolitan Height and Weight Tables (see Appendix 4, Appendix 5, and Appendix 6). Minimum body weight no less than 50 kg. Inclusion Criteria for Subjects with Normal Renal Function * Subjects who are in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, hepatitis B and C tests, and human immunodeficiency virus (HIV) testing. * Creatinine clearance \> 80 mL/min indicating normal renal function. Inclusion Criteria for Renally Impaired Subjects * Renally impaired subjects may be taking medications which, in the opinion of the clinical investigator and sponsor, are believed to be therapeutic for the subjects (but do not affect OPC-34712 absorption, distribution, metabolism, or elimination). Inhibitors and inducers of CYP3A4 and inhibitors of CYP2D6 are not allowed. * Creatinine clearance \< 30 mL/min indicating severe renal impairment. * Subjects with renal impairment should have relatively stable renal function as determined by creatinine clearance and otherwise be in generally good health.
Exclusion criteria
Clinically significant abnormality in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the subject at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. * Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion, or any other condition that may place the subject at risk. * History of drug and/or alcohol abuse within 2 years prior to Screening. * A positive urine alcohol test and/or urine drug screen for substance of abuse at Screening or upon check-in to the trial site. * The donation of blood or plasma within 30 days prior to dosing. * Any history of significant bleeding or hemorrhagic tendencies. * History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HCV). * History of acquired immunodeficiency syndrome or determined human immunodeficiency virus (HIV) positive at Screening. * Use of an investigational drug or product, or participation in a drug trial within 30 days prior to dosing. * Previous exposure to OPC-34712. * History of clinically significant drug allergies or sensitivities. * Subjects who are pregnant or breastfeeding. A negative serum pregnancy test must be confirmed prior to administration of trial medication for all female subjects. * Subjects who have a supine pulse rate, after resting for ≥ 3 minutes, outside the range of 40 to 90 bpm. The sponsor may allow exceptions if they are not deemed clinically significant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unbound Area Under the Concentration (AUC) Time Curve Calculated to the Last Observable Concentration Brexpiprazole (AUCt,u). | Day 1 to Day 8 | Blood samples were collected on Day 1 at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours Postdose or at Early Termination (ET). Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| Unbound Area Under AUC- Time Curve From Time Zero to Infinity (AUC∞,u). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| Unbound Maximum (Peak) Plasma Concentration of Brexpiprazole (Cmax,u). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cmax of Brexiprazole Metabolite (DM-3411) (Tmax). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Tmax is the time taken to reach highest measured concentration of the drug during the dosing interval. |
| Apparent Clearance From Plasma After Extravascular Administration of Brexpiprazole (CL/F). | Day 1 to Day 8 | The value of CL/F was determined as Dose/AUC∞. Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood. |
| Unbound Fraction of Brexpiprazole in Plasma (fu). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| Apparent Unbound Clearance From Plasma After Extravascular Administration of Brexpiprazole (CLu/F). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. The AUCt was estimated using the linear trapezoidal rule. |
| Renal Clearance (CLr) of Brexipiprazole Metabolite (DM-3411). | Day 1 to Day 8 | Urine samples were collected at Predose at intervals of 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| Fraction of the Systemically Available Brexpiprazole Metabolite (DM-3411) Excreted Into the Urine (fe,u). | Day 1 to Day 8 | Urine samples were collected at Predose and at intervals of 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | AEs were recorded from Screening (ICF was signed) to Follow-up 31 (+ 2) days. | An adverse event (AE) was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician. |
| Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
| AUC Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. The AUC∞ was estimated using the linear trapezoidal rule. |
| Maximum Plasma Concentration of Brexpiprazole Metabolite (DM-3411) (Cmax). | Day 1 to Day 8 | Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant. |
Countries
United States
Participant flow
Recruitment details
The trial was an open-label, multicenter, parallel-arm, single-dose trial in two groups: 1 group of participants with normal renal function and 1 group of severely renally impaired participants.
Pre-assignment details
The participant assignment was made based on Urine Creatinine Clearance (urine CLcr). If the urine CLcr was \< 30 mL/minute for renally impaired participants and the urine CLcr was \> 80 mL/minute for participants with normal renal function.
Participants by arm
| Arm | Count |
|---|---|
| Normal Participants with normal renal function were administered 3 mg brexpiprazole on Day 1. | 9 |
| Renally Impaired Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1. | 10 |
| Total | 19 |
Baseline characteristics
| Characteristic | Normal | Renally Impaired | Total |
|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 10.1 | 62.9 Years STANDARD_DEVIATION 12.2 | 60.9 Years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Unbound Area Under AUC- Time Curve From Time Zero to Infinity (AUC∞,u).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Unbound Area Under AUC- Time Curve From Time Zero to Infinity (AUC∞,u). | 9.58 ng*h/mL | Standard Deviation 2.26 |
| Renally Impaired | Unbound Area Under AUC- Time Curve From Time Zero to Infinity (AUC∞,u). | 18.0 ng*h/mL | Standard Deviation 8.72 |
Primary
Unbound Area Under the Concentration (AUC) Time Curve Calculated to the Last Observable Concentration Brexpiprazole (AUCt,u).
Blood samples were collected on Day 1 at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours Postdose or at Early Termination (ET). Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for pharmacokinetics (PK) analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Unbound Area Under the Concentration (AUC) Time Curve Calculated to the Last Observable Concentration Brexpiprazole (AUCt,u). | 8.17 nanograms*hours/mL (ng*h/mL) | Standard Deviation 1.37 |
| Renally Impaired | Unbound Area Under the Concentration (AUC) Time Curve Calculated to the Last Observable Concentration Brexpiprazole (AUCt,u). | 13.3 nanograms*hours/mL (ng*h/mL) | Standard Deviation 6.26 |
Primary
Unbound Maximum (Peak) Plasma Concentration of Brexpiprazole (Cmax,u).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Unbound Maximum (Peak) Plasma Concentration of Brexpiprazole (Cmax,u). | 0.195 ng/mL | Standard Deviation 0.0662 |
| Renally Impaired | Unbound Maximum (Peak) Plasma Concentration of Brexpiprazole (Cmax,u). | 0.198 ng/mL | Standard Deviation 0.0702 |
Secondary
Apparent Clearance From Plasma After Extravascular Administration of Brexpiprazole (CL/F).
The value of CL/F was determined as Dose/AUC∞. Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Apparent Clearance From Plasma After Extravascular Administration of Brexpiprazole (CL/F). | 23.0 mL/h/kg | Standard Deviation 8.05 |
| Renally Impaired | Apparent Clearance From Plasma After Extravascular Administration of Brexpiprazole (CL/F). | 14.2 mL/h/kg | Standard Deviation 6.46 |
Secondary
Apparent Unbound Clearance From Plasma After Extravascular Administration of Brexpiprazole (CLu/F).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Apparent Unbound Clearance From Plasma After Extravascular Administration of Brexpiprazole (CLu/F). | 0.110 mL/h/kg | Standard Deviation 0.0493 |
| Renally Impaired | Apparent Unbound Clearance From Plasma After Extravascular Administration of Brexpiprazole (CLu/F). | 0.0686 mL/h/kg | Standard Deviation 0.0336 |
Secondary
AUC Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. The AUC∞ was estimated using the linear trapezoidal rule.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations. AUC-time curve from zero to infinity (AUC∞) was not determined for DM-3411 metabolite.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | AUC Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞). | 2050 ng*h/mL | Standard Deviation 510 |
| Renally Impaired | AUC Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞). | 3800 ng*h/mL | Standard Deviation 1970 |
Secondary
AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. The AUCt was estimated using the linear trapezoidal rule.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt). | 1410 ng*h/mL | Standard Deviation 423 |
| Renally Impaired | AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt). | 2080 ng*h/mL | Standard Deviation 1230 |
Secondary
Fraction of the Systemically Available Brexpiprazole Metabolite (DM-3411) Excreted Into the Urine (fe,u).
Urine samples were collected at Predose and at intervals of 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Fraction of the Systemically Available Brexpiprazole Metabolite (DM-3411) Excreted Into the Urine (fe,u). | 3.91 % of unbound brexpiprazole in urine. | Standard Deviation 1.66 |
| Renally Impaired | Fraction of the Systemically Available Brexpiprazole Metabolite (DM-3411) Excreted Into the Urine (fe,u). | 2.55 % of unbound brexpiprazole in urine. | Standard Deviation 1.19 |
Secondary
Maximum Plasma Concentration of Brexpiprazole Metabolite (DM-3411) (Cmax).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Maximum Plasma Concentration of Brexpiprazole Metabolite (DM-3411) (Cmax). | 18.2 ng/mL | Standard Deviation 6.24 |
| Renally Impaired | Maximum Plasma Concentration of Brexpiprazole Metabolite (DM-3411) (Cmax). | 19.8 ng/mL | Standard Deviation 12.3 |
Secondary
Renal Clearance (CLr) of Brexipiprazole Metabolite (DM-3411).
Urine samples were collected at Predose at intervals of 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Renal Clearance (CLr) of Brexipiprazole Metabolite (DM-3411). | 1.38 mL/h/kg | Standard Deviation 0.883 |
| Renally Impaired | Renal Clearance (CLr) of Brexipiprazole Metabolite (DM-3411). | 0.683 mL/h/kg | Standard Deviation 0.471 |
Secondary
Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations. The terminal phase elimination half-life was not determined for DM-3411 metabolite.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z). | 71.7 h | Standard Deviation 23.8 |
| Renally Impaired | Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z). | 87.4 h | Standard Deviation 28.9 |
Secondary
The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion.
An adverse event (AE) was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Time frame: AEs were recorded from Screening (ICF was signed) to Follow-up 31 (+ 2) days.
Population: The dataset for all safety analyses consisted of the data from all enrolled participants who received at least 1 dose of study medication, regardless of any protocol deviation. All observed data for these subjects were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal | The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | Participants with adverse events | 3 participants |
| Normal | The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | Participants with TEAEs | 3 participants |
| Normal | The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | Participants with severe TEAEs | 0 participants |
| Renally Impaired | The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | Participants with adverse events | 5 participants |
| Renally Impaired | The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | Participants with TEAEs | 5 participants |
| Renally Impaired | The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion. | Participants with severe TEAEs | 1 participants |
Secondary
Time to Cmax of Brexiprazole Metabolite (DM-3411) (Tmax).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Tmax is the time taken to reach highest measured concentration of the drug during the dosing interval.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal | Time to Cmax of Brexiprazole Metabolite (DM-3411) (Tmax). | 12.0 h |
| Renally Impaired | Time to Cmax of Brexiprazole Metabolite (DM-3411) (Tmax). | 30.0 h |
Secondary
Unbound Fraction of Brexpiprazole in Plasma (fu).
Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time frame: Day 1 to Day 8
Population: The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal | Unbound Fraction of Brexpiprazole in Plasma (fu). | 0.476 % of unbound brexpiprazole in plasma | Standard Deviation 0.0525 |
| Renally Impaired | Unbound Fraction of Brexpiprazole in Plasma (fu). | 0.492 % of unbound brexpiprazole in plasma | Standard Deviation 0.0346 |