Schizophrenia, Cerebellar Ataxia
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine the safety, tolerability and pharmacokinetics (PK) of single and multiple rising doses of TAK-831 in healthy participants.
Detailed description
The drug being tested in this study is called TAK-831. TAK-831 is being tested to treat participant who have schizophrenia and cerebellar ataxia. This study will look at the PK, safety and tolerability of TAK-831 in healthy participants. The study will enroll approximately 120 participants. The study will include 4 parts: Part 1 (single-rising dose \[SRD\]), Part 2 (SRD/multiple-rising dose \[MRD\]), Part 3 (MRD) and Part 4 (relative bioavailability study). Participants will be randomly assigned (by chance, like flipping a coin) to receive either active drug TAK-831 or placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Part 1, Cohort 1: single dose of TAK-831 100 mg * Part 1, Cohort 2: single dose of TAK-831 250 mg * Part 1, Cohort 3: single dose of TAK-831 500 mg * Part 1, Cohort 4: single dose of TAK-831 30 mg * Part 1, Cohort 5: single dose of TAK-831 750 mg * Part 1, Cohort 6: single dose of TAK-831 10 mg * Part 2, Cohort 1: single dose of TAK-831 30 mg * Part 2, Cohort 2: single dose of TAK-831 100 mg * Part 2, Cohort 3: single dose of TAK-831 200 mg * Part 2, Cohort 4: single dose of TAK-831 400 mg * Part 3, Cohort 1: TAK-831 400 mg * Part 4: TAK-831 100 mg (Tablet Fasted + Tablet Fed + Suspension Fasted) * Part 4: TAK-831 100 mg (Tablet Fed + Tablet Fasted + Suspension Fasted) * Part 4: TAK-831 100 mg (Suspension Fasted+ Tablet Fed + Tablet Fasted) Dosing with TAK-831 will progress into study Part 2, 3 and 4, only after review of all available safety, tolerability, and PK data collected in Cohorts 1 to 6 of the Study Part 1. This single center trial will be conducted in the United Kingdom. The overall time to participate in this study is approximately up to 58 days. Participants will be admitted in the clinic for the up to 20 days, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment. The study was terminated by Takeda due to the discomfort observed in the study participants from the CSF collection procedure in Part 3 of the study, hence it is was not feasible to collect further CSF samples that were required to meet the exploratory objectives of the study. Part 1, 2 and 4 of the study were completed as planned.
Interventions
DRUGTAK-831 Oral Suspension
TAK-831 oral suspension.
DRUGTAK-831 Placebo
TAK-831 placebo-matching oral suspension.
DRUGTAK-831 Tablet
TAK-831 tablet.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Should be capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Healthy male or female aged between 18 to 55 years- Weighing at least 45 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m\^2). 4. Male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 5. Female participant with no childbearing potential, defined as a participant that has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who is post menopausal (defined as continuous amenorrhea of at least 2 years and follicle-stimulating hormone \[FSH\] greater than \[\>\] 40 international units per liter \[IU/L\]).
Exclusion criteria
1. Received any investigational compound within 3 months prior to randomization. 2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress. 3. Has uncontrolled, clinically significant neurological (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality. 4. Has a known hypersensitivity to any component of the formulation of TAK-831. 5. Female participant is of childbearing potential. 6. Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in. 7. History of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or 1 single measure of spirits or 1 small glass of wine. 8. Has taken any excluded medication, supplements, or food products during the time periods listed in the excluded medications and dietary products. 9. Female participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. 10. Male participant intending to donate sperm during the course of this study or for 12 weeks after the last dose of study medication. 11. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma, hypoxemia, hypertension, seizures, or allergic skin rash. 12. Has a QT interval with Fridericia's correction method (QTcF) \>450 millisecond (msec) (males) or \>470 msec (females) or PR outside the range of 120 to 220 msec, confirmed with one repeat testing, at the screening visit or check-in (Day -2). 13. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention. 14. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1. 15. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody/antigen at Screening. 16. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in. Cotinine test is positive at Screening or Check-in. 17. Has poor peripheral venous access. 18. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to first dose of medication. 19. Has a Screening or Check-in abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator or designee. 20. Has a supine blood pressure outside the ranges of 90 to 140 millimeter of mercury (mm Hg) for systolic and 50 to 90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in. 21. Has a resting heart rate outside the range 40 to 100 bpm confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in. 22. Has abnormal Screening or check-in laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \>1.5 the upper limits of normal. 23. Has a risk of suicide according to the Investigator's clinical judgment (example, per The Columbia Suicide Severity Rating Scale \[C-SSRS\]), or has scored yes on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or yes on any item of the Suicidal Behavior section, except for the Non-Suicidal Self-Injurious Behavior, if this behaviour occurred in the past 2 years. 24. Has received TAK-831 in a previous clinical study. 25. Participant is vegan or vegetarian (Part 4 only - food effect).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Baseline up to 30 days after the last dose of study drug (Part 1 Day 31, Part 2 Day 46, Part 3 Day 44 and Part 4 Day 43) | — |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Baseline up to Day 15 in Part 1, Day 30 in Part 2, Day 28 in Part 3 and Day 25 in Part 4 | Clinical laboratory tests included hematology, serum chemistry and urinalysis. |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Baseline up to Day 15 in Part 1, Day 30 in Part 2, Day 28 in Part 3 and Day 25 in Part 4 | Markedly abnormal criteria for vital signs measurement was assessed. The lower criteria and upper criteria for abnormality are as follow: systolic blood pressure at less than (\<) 85 millimeter of mercury (mm Hg) to greater than (\>) 180 mm Hg; diastolic blood pressure \< 50 mm Hg to \>110 mm Hg; pulse rate \<50 bpm to \>120 bpm; Temperature \<35.6 degree Celsius to \>37.7 degree Celsius. |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | Baseline up to Day 15 in Part 1, Day 30 in Part 2, Day 28 in Part 3 and Day 25 in Part 4 | Markedly abnormal criteria for ECG was assessed. The lower cut-off point criteria and upper cut-off point criteria are as follow: heart rate \<50 beats per minute (bpm) to \>120 bpm; PR interval less than or equal to (\<=) 80 millisecond (msec) to greater than or equal to (\>=) 200 msec; QRS interval \<=80 msec to \>=180 msec; QT interval \<=300 msec to \>=460 msec; QTcB interval \<=300 msec to \>=500 msec or \>=30 msec change from baseline and \>=450 msec; QT interval with Fridericia's correction method (QTcF) interval \<=50 msec to \>=500 msec or \>=30 msec change from baseline and \>=450 msec. |
Secondary
| Measure | Time frame |
|---|---|
| Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose |
| Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose |
| Part 2 and 3: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-831 | Day 16 (Part 2) and Day 14 (Part 3) pre-dose and at multiple time points (up to 24 hours) post-dose |
| Part 2 and 3: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-831 | Day 16 (Part 2) and Day 14 (Part 3) pre-dose and at multiple time points (up to 24 hours) post-dose |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose; Day 16 (Part 2) and Day 14 (Part 3) pre-dose and at multiple time points (up to 24 hours) post-dose |
| Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United Kingdom from 23 September 2015 to 12 July 2016.
Pre-assignment details
Healthy participants were enrolled in 4 part study to receive TAK-831: single rising dose (SRD) in Part 1; SRD/multiple rising dose (MRD) in Part 2; MRD in Part 3; relative bioavailability(rBA) in 3-sequence crossover in Part 4. Part 3 was terminated due to discomfort observed in participants from the cerebrospinal fluid (CSF) collection procedure.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Pooled TAK-831 placebo-matching suspension, orally, once on Day 1. | 12 |
| Part 1: TAK-831 10 mg TAK-831 10 milligram (mg), suspension, orally, once on Day 1. | 6 |
| Part 1: TAK-831 30 mg TAK-831 30 mg, suspension, orally, once on Day 1. | 6 |
| Part 1: TAK-831 100 mg TAK-831 100 mg, suspension, orally, once on Day 1. | 6 |
| Part 1: TAK-831 250 mg TAK-831 250 mg, suspension, orally, once on Day 1. | 6 |
| Part 1: TAK-831 500 mg TAK-831 500 mg, suspension, orally, once on Day 1. | 6 |
| Part 1: TAK-831 750 mg TAK-831 750 mg, suspension, orally, once on Day 1. | 6 |
| Part 2: Placebo Pooled TAK-831 placebo-matching suspension, orally, once on Day 1 and Days 4-16. | 8 |
| Part 2: TAK-831 30 mg TAK-831 30 mg, suspension, orally, once on Day 1 and Days 4-16. | 6 |
| Part 2: TAK-831 100 mg TAK-831 100 mg, suspension, orally, once on Day 1 and Days 4-16. | 6 |
| Part 2: TAK-831 200 mg TAK-831 200 mg, suspension, orally, once on Day 1 and Days 4-16. | 6 |
| Part 2: TAK-831 400 mg TAK-831 400 mg, suspension, orally, once on Day 1 and Days 4-16. | 6 |
| Part 3: Placebo TAK-831 placebo-matching suspension, orally, once daily on Days 1-14. | 1 |
| Part 3: TAK-831 400 mg TAK-831 400 mg, suspension, orally, once daily from Days 1-14. | 5 |
| Part 4: TAK-831 (Tablet Fasted+Tablet Fed+Suspension Fasted) TAK-831 100 mg, tablet, orally, in fasted state, once on Day 1 of Period 1, followed by a 5-day washout period, further followed by TAK-831 100 mg, tablet, orally, in fed state, once on Day 1 of Period 2, followed by a 5-day washout period, further followed by TAK-831 100 mg, suspension, orally, in fasted state, once on Day 1 of Period 3. | 8 |
| Part 4: TAK-831 (Tablet Fed+Tablet Fasted+Suspension Fasted) TAK-831 100 mg, tablet, orally, in fed state, once on Day 1 of Period 1, followed by a 5-day washout period, further followed by TAK-831 100 mg, tablet, orally, in fasted state, once on Day 1 of Period 2, followed by a 5-day washout period, further followed by TAK-831 100 mg, suspension, orally, in fasted state, once on Day 1 of Period 3. | 8 |
| Part 4: TAK-831 (Suspension Fasted+Tablet Fed+Tablet Fasted) TAK-831 100 mg, suspension, orally, in fasted state, once on Day 1 of Period 1, followed by a 5-day washout period, further followed by TAK-831 100 mg, tablet, orally, in fed state, once on Day 1 of Period 2, followed by a 5-day washout interval, further followed by TAK-831 100 mg, tablet, orally, in fasted state, once on Day 1 of Period 3. | 8 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All Parts | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 0 |
| All Parts | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| All Parts | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Crossover Treatment (Part 4: 1 Day) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Placebo Pooled | Part 1: TAK-831 10 mg | Part 1: TAK-831 30 mg | Part 1: TAK-831 100 mg | Part 1: TAK-831 250 mg | Part 1: TAK-831 500 mg | Part 1: TAK-831 750 mg | Part 2: Placebo Pooled | Part 2: TAK-831 30 mg | Part 2: TAK-831 100 mg | Part 2: TAK-831 200 mg | Part 2: TAK-831 400 mg | Part 3: Placebo | Part 3: TAK-831 400 mg | Part 4: TAK-831 (Tablet Fasted+Tablet Fed+Suspension Fasted) | Part 4: TAK-831 (Tablet Fed+Tablet Fasted+Suspension Fasted) | Part 4: TAK-831 (Suspension Fasted+Tablet Fed+Tablet Fasted) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 55 years | 12 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | 6 participants | 6 participants | 6 participants | 6 participants | 1 participants | 5 participants | 8 participants | 8 participants | 8 participants | 110 participants |
| Alcohol history Current drinker | 9 participants | 5 participants | 3 participants | 4 participants | 5 participants | 5 participants | 2 participants | 5 participants | 2 participants | 3 participants | 6 participants | 6 participants | 0 participants | 2 participants | 6 participants | 7 participants | 7 participants | 77 participants |
| Alcohol history Never drunk | 3 participants | 1 participants | 3 participants | 2 participants | 1 participants | 1 participants | 4 participants | 3 participants | 4 participants | 3 participants | 0 participants | 0 participants | 1 participants | 3 participants | 2 participants | 1 participants | 1 participants | 33 participants |
| Caffeine Consumption Caffeine consumption | 10 participants | 6 participants | 4 participants | 5 participants | 5 participants | 4 participants | 6 participants | 3 participants | 3 participants | 4 participants | 4 participants | 4 participants | 1 participants | 3 participants | 8 participants | 4 participants | 4 participants | 78 participants |
| Caffeine Consumption No caffeine consumption | 2 participants | 0 participants | 2 participants | 1 participants | 1 participants | 2 participants | 0 participants | 5 participants | 3 participants | 2 participants | 2 participants | 2 participants | 0 participants | 2 participants | 0 participants | 4 participants | 4 participants | 32 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 5 Participants | 6 Participants | 1 Participants | 4 Participants | 6 Participants | 7 Participants | 8 Participants | 93 Participants |
| Region of Enrollment United Kingdom | 12 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | 6 participants | 6 participants | 6 participants | 6 participants | 1 participants | 5 participants | 8 participants | 8 participants | 8 participants | 110 participants |
| Sex/Gender, Customized Male | 12 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | 6 participants | 6 participants | 6 participants | 6 participants | 1 participants | 5 participants | 8 participants | 8 participants | 8 participants | 110 participants |
| Smoking History Ex-smoker | 4 participants | 2 participants | 1 participants | 1 participants | 3 participants | 3 participants | 0 participants | 3 participants | 1 participants | 1 participants | 2 participants | 1 participants | 0 participants | 1 participants | 0 participants | 3 participants | 2 participants | 28 participants |
| Smoking History Never smoked | 8 participants | 4 participants | 5 participants | 5 participants | 3 participants | 3 participants | 6 participants | 5 participants | 5 participants | 5 participants | 4 participants | 5 participants | 1 participants | 4 participants | 8 participants | 5 participants | 6 participants | 82 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 12 | 2 / 6 | 2 / 6 | 2 / 6 | 1 / 6 | 3 / 6 | 4 / 6 | 6 / 8 | 5 / 6 | 6 / 6 | 2 / 6 | 5 / 6 | 1 / 1 | 5 / 5 | 5 / 23 | 3 / 23 | 4 / 24 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 1 | 0 / 5 | 0 / 23 | 0 / 23 | 0 / 24 |
Outcome results
Primary
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Baseline up to 30 days after the last dose of study drug (Part 1 Day 31, Part 2 Day 46, Part 3 Day 44 and Part 4 Day 43)
Population: The safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo Pooled | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 50.0 percentage of participants |
| Part 1: TAK-831 10 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 1: TAK-831 30 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 1: TAK-831 100 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 1: TAK-831 250 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| Part 1: TAK-831 500 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 50.0 percentage of participants |
| Part 1: TAK-831 750 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 2: Placebo Pooled | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 75.0 percentage of participants |
| Part 2: TAK-831 30 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Part 2: TAK-831 100 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 100.0 percentage of participants |
| Part 2: TAK-831 200 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 2: TAK-831 400 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Part 3: Placebo | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 100.0 percentage of participants |
| Part 3: TAK-831 400 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 100.0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 21.7 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fed | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 13.0 percentage of participants |
| Part 4: TAK-831 100 mg Suspension Fasted | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
Primary
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose
Markedly abnormal criteria for ECG was assessed. The lower cut-off point criteria and upper cut-off point criteria are as follow: heart rate \<50 beats per minute (bpm) to \>120 bpm; PR interval less than or equal to (\<=) 80 millisecond (msec) to greater than or equal to (\>=) 200 msec; QRS interval \<=80 msec to \>=180 msec; QT interval \<=300 msec to \>=460 msec; QTcB interval \<=300 msec to \>=500 msec or \>=30 msec change from baseline and \>=450 msec; QT interval with Fridericia's correction method (QTcF) interval \<=50 msec to \>=500 msec or \>=30 msec change from baseline and \>=450 msec.
Time frame: Baseline up to Day 15 in Part 1, Day 30 in Part 2, Day 28 in Part 3 and Day 25 in Part 4
Population: The safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 8.3 percentage of participants |
| Part 1: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 41.7 percentage of participants |
| Part 1: TAK-831 10 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 33.3 percentage of participants |
| Part 1: TAK-831 10 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 50.0 percentage of participants |
| Part 1: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 16.7 percentage of participants |
| Part 1: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 0 percentage of participants |
| Part 1: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 16.7 percentage of participants |
| Part 1: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 50.0 percentage of participants |
| Part 1: TAK-831 250 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 0 percentage of participants |
| Part 1: TAK-831 250 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 16.7 percentage of participants |
| Part 1: TAK-831 500 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 33.3 percentage of participants |
| Part 1: TAK-831 500 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 33.3 percentage of participants |
| Part 1: TAK-831 750 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 16.7 percentage of participants |
| Part 1: TAK-831 750 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 16.7 percentage of participants |
| Part 2: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 25.0 percentage of participants |
| Part 2: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 37.5 percentage of participants |
| Part 2: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 50.0 percentage of participants |
| Part 2: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 33.3 percentage of participants |
| Part 2: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 50.0 percentage of participants |
| Part 2: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 16.7 percentage of participants |
| Part 2: TAK-831 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 16.7 percentage of participants |
| Part 2: TAK-831 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 0 percentage of participants |
| Part 2: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 16.7 percentage of participants |
| Part 2: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 16.7 percentage of participants |
| Part 3: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 0 percentage of participants |
| Part 3: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 0 percentage of participants |
| Part 3: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 20.0 percentage of participants |
| Part 3: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 8.7 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 13.0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 21.7 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 13.0 percentage of participants |
| Part 4: TAK-831 100 mg Suspension Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | > upper cut-off point criteria | 12.5 percentage of participants |
| Part 4: TAK-831 100 mg Suspension Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | < lower cut-off point criteria | 16.7 percentage of participants |
Primary
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
Clinical laboratory tests included hematology, serum chemistry and urinalysis.
Time frame: Baseline up to Day 15 in Part 1, Day 30 in Part 2, Day 28 in Part 3 and Day 25 in Part 4
Population: The safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 1: TAK-831 10 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 1: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 1: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 1: TAK-831 250 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 1: TAK-831 500 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 1: TAK-831 750 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 16.7 percentage of participants |
| Part 2: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 2: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 2: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 33.3 percentage of participants |
| Part 2: TAK-831 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 2: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 3: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 3: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
| Part 4: TAK-831 100 mg Suspension Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 percentage of participants |
Primary
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
Markedly abnormal criteria for vital signs measurement was assessed. The lower criteria and upper criteria for abnormality are as follow: systolic blood pressure at less than (\<) 85 millimeter of mercury (mm Hg) to greater than (\>) 180 mm Hg; diastolic blood pressure \< 50 mm Hg to \>110 mm Hg; pulse rate \<50 bpm to \>120 bpm; Temperature \<35.6 degree Celsius to \>37.7 degree Celsius.
Time frame: Baseline up to Day 15 in Part 1, Day 30 in Part 2, Day 28 in Part 3 and Day 25 in Part 4
Population: The safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 50.0 percentage of participants |
| Part 1: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 8.3 percentage of participants |
| Part 1: TAK-831 10 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 50.0 percentage of participants |
| Part 1: TAK-831 10 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 1: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 16.7 percentage of participants |
| Part 1: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 1: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 16.7 percentage of participants |
| Part 1: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 1: TAK-831 250 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 1: TAK-831 250 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 0 percentage of participants |
| Part 1: TAK-831 500 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 1: TAK-831 500 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 33.3 percentage of participants |
| Part 1: TAK-831 750 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 16.7 percentage of participants |
| Part 1: TAK-831 750 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 2: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 87.5 percentage of participants |
| Part 2: Placebo Pooled | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 2: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 66.7 percentage of participants |
| Part 2: TAK-831 30 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 2: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 83.3 percentage of participants |
| Part 2: TAK-831 100 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 16.7 percentage of participants |
| Part 2: TAK-831 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 33.3 percentage of participants |
| Part 2: TAK-831 200 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 2: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 33.3 percentage of participants |
| Part 2: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 83.3 percentage of participants |
| Part 3: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 0 percentage of participants |
| Part 3: Placebo | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 100.0 percentage of participants |
| Part 3: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 60.0 percentage of participants |
| Part 3: TAK-831 400 mg | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 20.0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 13.0 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 4.3 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 17.4 percentage of participants |
| Part 4: TAK-831 100 mg Tablet Fed | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 8.7 percentage of participants |
| Part 4: TAK-831 100 mg Suspension Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | < lower criteria | 29.2 percentage of participants |
| Part 4: TAK-831 100 mg Suspension Fasted | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | > greater criteria | 12.5 percentage of participants |
Secondary
Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose
Population: The PK set included all participants with at least 1 estimable PK parameter for TAK-831.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo Pooled | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 109.7 ng*hr/mL | Standard Deviation 22.02 |
| Part 1: TAK-831 10 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 499.2 ng*hr/mL | Standard Deviation 92.57 |
| Part 1: TAK-831 30 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 1271.4 ng*hr/mL | Standard Deviation 253.26 |
| Part 1: TAK-831 100 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 1945.5 ng*hr/mL | Standard Deviation 294.36 |
| Part 1: TAK-831 250 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 4140.7 ng*hr/mL | Standard Deviation 1602.32 |
| Part 1: TAK-831 500 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 5512.0 ng*hr/mL | Standard Deviation 1721.84 |
| Part 1: TAK-831 750 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 342.9 ng*hr/mL | Standard Deviation 46.8 |
| Part 2: Placebo Pooled | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 980.5 ng*hr/mL | Standard Deviation 204.04 |
| Part 2: TAK-831 30 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 2092.7 ng*hr/mL | Standard Deviation 273.06 |
| Part 2: TAK-831 100 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 2866.6 ng*hr/mL | Standard Deviation 822.22 |
| Part 2: TAK-831 200 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 653.7 ng*hr/mL | Standard Deviation 308.86 |
| Part 2: TAK-831 400 mg | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 1428.8 ng*hr/mL | Standard Deviation 433.24 |
| Part 3: Placebo | Part 1, 2 and 4: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 1115.3 ng*hr/mL | Standard Deviation 296.56 |
Comparison: Dose proportionality was evaluated using the following power model: ln (PK Parameter) = a+b\*ln (dose), where a and b are the intercept and slope of the line, respectively. Dose proportionality was declared when the 90 % CI of the slope lies entirely within the critical region (0.9483, 1.0517) for the dose range of 10 mg to 750 mg.p-value: <0.00190% CI: [0.7925, 0.9084]Power model
Comparison: Dose proportionality was evaluated using the following power model: ln (PK Parameter) = a+b\*ln (dose), where a and b were the intercept and slope of the line, respectively. Dose proportionality was declared when the 90% CI of the slope lies entirely within the critical region (0.9139, 1.0861) for the dose range of 30 mg to 400 mg.p-value: <0.00190% CI: [0.7618, 0.9212]Power model
Comparison: The point estimate and CI were obtained by taking the antilog of the difference in the log transformed LS Means.90% CI: [0.4797, 0.6149]
Comparison: The point estimate and CI were obtained by taking the antilog of the difference in the log transformed LS Means.90% CI: [1.9592, 2.7854]
Secondary
Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose
Population: The PK set included all participants with at least 1 estimable PK parameter for TAK-831.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo Pooled | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 98.0 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 17.02 |
| Part 1: TAK-831 10 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 463.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 80.13 |
| Part 1: TAK-831 30 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 1186.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 256.67 |
| Part 1: TAK-831 100 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 1900.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 293.72 |
| Part 1: TAK-831 250 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 4111.1 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1599.18 |
| Part 1: TAK-831 500 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 5374.0 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1651.36 |
| Part 1: TAK-831 750 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 296.3 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 95.31 |
| Part 2: Placebo Pooled | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 938.4 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 180.29 |
| Part 2: TAK-831 30 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 2030.2 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 265.73 |
| Part 2: TAK-831 100 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 2832.7 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 819.36 |
| Part 2: TAK-831 200 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 598.6 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 310.31 |
| Part 2: TAK-831 400 mg | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 1397.7 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 434.45 |
| Part 3: Placebo | Part 1, 2 and 4: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | 1083.6 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 302.13 |
Comparison: Dose proportionality was evaluated using the following power model: ln (PK Parameter) = a+b\*ln (dose), where a and b are the intercept and slope of the line, respectively. Dose proportionality was declared when the 90 % CI of the slope lies entirely within the critical region (0.9483, 1.0517) for the dose range of 10 mg to 750 mg.90% CI: [0.8145, 0.9296]
Comparison: Dose proportionality was evaluated using the following power model: ln (PK Parameter) = a+b\*ln (dose), where a and b were the intercept and slope of the line, respectively. Dose proportionality was declared when the 90% CI of the slope lies entirely within the critical region (0.9139, 1.0861) for the dose range of 30 mg to 400 mg.90% CI: [0.8062, 1.0209]Power model
Comparison: The point estimate and CI were obtained by taking the antilog of the difference in the log transformed LS Means.90% CI: [0.4324, 0.5777]
Comparison: The point estimate and CI were obtained by taking the antilog of the difference in the log transformed LS Means.90% CI: [2.1, 3.1275]
Secondary
Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose
Population: The PK set included all participants with at least 1 estimable PK parameter for TAK-831.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo Pooled | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 90.7 nanogram per milliliter (ng/mL) | Standard Deviation 26.95 |
| Part 1: TAK-831 10 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 313.3 nanogram per milliliter (ng/mL) | Standard Deviation 121.97 |
| Part 1: TAK-831 30 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 567.7 nanogram per milliliter (ng/mL) | Standard Deviation 218.76 |
| Part 1: TAK-831 100 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 905.8 nanogram per milliliter (ng/mL) | Standard Deviation 329.53 |
| Part 1: TAK-831 250 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1304.5 nanogram per milliliter (ng/mL) | Standard Deviation 402.89 |
| Part 1: TAK-831 500 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 2121.7 nanogram per milliliter (ng/mL) | Standard Deviation 554.92 |
| Part 1: TAK-831 750 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 167.1 nanogram per milliliter (ng/mL) | Standard Deviation 39.95 |
| Part 2: Placebo Pooled | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 467.2 nanogram per milliliter (ng/mL) | Standard Deviation 84.36 |
| Part 2: TAK-831 30 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1087.3 nanogram per milliliter (ng/mL) | Standard Deviation 398.76 |
| Part 2: TAK-831 100 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1095.5 nanogram per milliliter (ng/mL) | Standard Deviation 236.86 |
| Part 2: TAK-831 200 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 216.0 nanogram per milliliter (ng/mL) | Standard Deviation 104.68 |
| Part 2: TAK-831 400 mg | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 377.7 nanogram per milliliter (ng/mL) | Standard Deviation 175.9 |
| Part 3: Placebo | Part 1, 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-831 | 594.1 nanogram per milliliter (ng/mL) | Standard Deviation 288.77 |
Comparison: Dose proportionality was evaluated using the following power model: ln (PK Parameter) is equal to (=) a+b\*ln (dose), where a and b are the intercept and slope of the line, respectively. Dose proportionality was declared when the 90 percent (%) confidence interval (CI) of the slope lies entirely within the critical region (0.9483, 1.0517) for the dose range of 10 mg to 750 mg.90% CI: [0.5969, 0.7355]
Comparison: Dose proportionality was evaluated using the following power model: ln (PK Parameter) = a+b\*ln (dose), where a and b were the intercept and slope of the line, respectively. Dose proportionality was declared when the 90% CI of the slope lies entirely within the critical region (0.9139, 1.0861) for the dose range of 30 mg to 400 mg.90% CI: [0.6597, 0.8993]Power model
Comparison: The point estimate and CI were obtained by taking the antilog of the difference in the log transformed lease square (LS) Means.90% CI: [0.3043, 0.4301]
Comparison: The point estimate and CI were obtained by taking the antilog of the difference in the log transformed LS Means.90% CI: [1.4625, 2.2116]
Secondary
Part 2 and 3: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-831
Time frame: Day 16 (Part 2) and Day 14 (Part 3) pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants with at least 1 estimable PK parameter for TAK-831. Due to discomfort observed in participants from the CSF collection procedure, Part 3 of the study was terminated hence no participants were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo Pooled | Part 2 and 3: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-831 | 319.8 ng*hr/mL | Standard Deviation 83.06 |
| Part 1: TAK-831 10 mg | Part 2 and 3: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-831 | 1211.0 ng*hr/mL | Standard Deviation 236.45 |
| Part 1: TAK-831 30 mg | Part 2 and 3: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-831 | 1973.0 ng*hr/mL | Standard Deviation 316.34 |
| Part 1: TAK-831 100 mg | Part 2 and 3: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-831 | 3452.6 ng*hr/mL | Standard Deviation 1249.58 |
Secondary
Part 2 and 3: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-831
Time frame: Day 16 (Part 2) and Day 14 (Part 3) pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants with at least 1 estimable PK parameter for TAK-831. Due to discomfort observed in participants from the CSF collection procedure, Part 3 of the study was terminated hence no participants were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo Pooled | Part 2 and 3: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-831 | 177.5 ng/mL | Standard Deviation 45.85 |
| Part 1: TAK-831 10 mg | Part 2 and 3: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-831 | 560.7 ng/mL | Standard Deviation 214.9 |
| Part 1: TAK-831 30 mg | Part 2 and 3: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-831 | 897.7 ng/mL | Standard Deviation 192.73 |
| Part 1: TAK-831 100 mg | Part 2 and 3: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for TAK-831 | 1269.5 ng/mL | Standard Deviation 451.37 |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours in Part 1 and up to 72 hours in Part 2 and 4) post-dose; Day 16 (Part 2) and Day 14 (Part 3) pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants with at least 1 estimable PK parameter for TAK-831. Due to discomfort observed in participants from the CSF collection procedure, Part 3 of the study was terminated hence no participants were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Placebo Pooled | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.250 hours |
| Part 1: Placebo Pooled | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 1: TAK-831 10 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 1: TAK-831 10 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.260 hours |
| Part 1: TAK-831 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.435 hours |
| Part 1: TAK-831 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 1: TAK-831 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.275 hours |
| Part 1: TAK-831 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 1: TAK-831 250 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.725 hours |
| Part 1: TAK-831 250 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 1: TAK-831 500 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 1: TAK-831 500 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.760 hours |
| Part 1: TAK-831 750 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | 0.500 hours |
| Part 1: TAK-831 750 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.500 hours |
| Part 2: Placebo Pooled | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.500 hours |
| Part 2: Placebo Pooled | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | 0.365 hours |
| Part 2: TAK-831 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.375 hours |
| Part 2: TAK-831 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | 0.500 hours |
| Part 2: TAK-831 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.500 hours |
| Part 2: TAK-831 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | 0.490 hours |
| Part 3: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 3: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.930 hours |
| Part 3: TAK-831 400 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 3.980 hours |
| Part 3: TAK-831 400 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |
| Part 4: TAK-831 100 mg Tablet Fasted | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.250 hours |
| Part 4: TAK-831 100 mg Tablet Fasted | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 16 | NA hours |