Phase 1 TAK-041 First-in-Human Safety, Tolerability, and Pharmacokinetics Study

Sponsor

Neurocrine Biosciences (Industry)

Overall Status

Completed

CT.gov ID

NCT02748694

Collaborator

Takeda (Industry)

114

Enrollment

Location

Arms

40.4

Actual Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TAK-041:

Following oral single and multiple doses in healthy participants.
As add-on therapy to antipsychotics in stable schizophrenia participants.
To determine the oral bioavailability of the TAK-041 tablet formulation compared to the oral suspension formulation in the fasted state.
To assess the effect of food on the PK of TAK-041 in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers Schizophrenia	Drug: TAK-041 Drug: TAK-041 Placebo	Phase 1

Detailed Description

The drug being tested in this study is called TAK-041. TAK-041 is being tested to evaluate its safety, tolerability, and PK of single and multiple doses in healthy participants and as add-on therapy to antipsychotics in participants with stable schizophrenia. This study will also assess the oral bioavailability in healthy participants administered with tablet formulation compared to oral suspension formulation in fasted state, and effect of high-fat, high-calorie meal on the PK of single dose of TAK-041 tablet formulation.

The study will enroll approximately 114 participants. The study is composed of 4 parts. Part 1 (single-rising dose [SRD], alternating panel design and a sequential panel design), Part 2 (multiple-rising dose [MRD], sequential panel design), Part 3 (open label parallel design), and Part 4 (single dose cohort).

Part 1 consists of 5 cohorts, participants in Cohorts 1 and 2 will be randomly assigned (by chance, like flipping a coin) to treatment sequences of 2 periods and for Cohorts 3 to 5 participants will be assigned to a single dose sequential-panel:

TAK-041 5-160 mg
Placebo (inactive) - this is a similar formulation that looks like the study drug but has no active ingredient.

Part 2 consists of 4 cohorts, participants will be randomly assigned to one of the two treatments:

TAK-041
Placebo Dose levels for Part 2 cohort 1 will be based on emerging safety/tolerability and PK data from Part 1. The dose levels for Part 2 Cohorts 2 onwards will be based on emerging safety/tolerability and available PK data from Part 1 and from preceding cohorts in Part 2.

Part 3 consists of 2 cohorts, participants will be randomly assigned to one of the two treatments under fasted state or fed state:

TAK-041 40 mg tablet (Fasted state)
TAK-041 40 mg tablet (Fed state)

Part 4 consists of 1 cohort, participants will be randomly assigned to one of the two treatments:

TAK-041
Placebo The dose levels for Part 4 will be based upon the emerging safety/tolerability and PK data of same dose in healthy participants from Part 2.

This single center trial will be conducted in the United States. Participants will remain confined to the study site from check-in (Day -1) through Days 5 of each period in Part 1, on Days -2 to 3, Days 7 to 10, Days 14 to 17, Day 21 to 24 in Part 2, on Days 1 to 3 in Part 3, and on Days -2 to 3, Days 7 to 10, Days 14 to 17, Days 21 to 24 in Part 4. A final visit that completes the study will occur 12 to 16 days after the last safety and PK follow-up visit in Part 1, 2 and 4, and 18 days after dosing in Part 3.

Study Design

Study Type:

Interventional

Actual Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Other

Official Title:

A Randomized, Double -Blind, Placebo-Controlled, Phase 1, Ascending Oral Single and Multiple Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-041 in Healthy Subjects and Subjects With Stable Schizophrenia and a Randomized Open-Label, Single Dose, Parallel Design to Evaluate the Relative Bioavailability and Effect of Food on the Pharmacokinetics of TAK-041 Tablet Formulation in Healthy Subjects

Actual Study Start Date :

May 9, 2016

Actual Primary Completion Date :

Sep 22, 2019

Actual Study Completion Date :

Sep 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Part 1 (SRD): Placebo Cohorts 1-5 TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	Drug: TAK-041 Placebo TAK-041 placebo-matching suspension or tablet.
Experimental: Part 1 (SRD): Cohort 1: TAK-041 5/20 mg TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 20 mg, suspension, orally, once on Day 8 in the SRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 1 (SRD): Cohort 2: TAK-041 10/40 mg TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 40 mg, suspension, orally, once on Day 8 in the SRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 1 (SRD): Cohort 3: TAK-041 80 mg TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 1 (SRD): Cohort 4: TAK-041 120 mg TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 1 (SRD): Cohort 5: TAK-041 160 mg TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Placebo Comparator: Part 2 (MRD): Placebo Cohorts 1-4 TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the multiple-rising dose (MRD) period.	Drug: TAK-041 Placebo TAK-041 placebo-matching suspension or tablet.
Experimental: Part 2 (MRD): Cohort 1: TAK-041 40/20 mg TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 2 (MRD): Cohort 2: TAK-041 80/40 mg TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 2 (MRD): Cohort 3: TAK-041 120/60 mg TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 2 (MRD): Cohort 4: TAK-041 160/80 mg TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Experimental: Part 3: RBA/Food Effect: Regimen B TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	Drug: TAK-041 TAK-041 tablets or oral suspension.
Placebo Comparator: Part 4: MRD: Placebo TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	Drug: TAK-041 TAK-041 tablets or oral suspension. Drug: TAK-041 Placebo TAK-041 placebo-matching suspension or tablet.
Experimental: Part 4: MRD: TAK-041 160/80 mg TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.	Drug: TAK-041 TAK-041 tablets or oral suspension.

Outcome Measures

Primary Outcome Measures

Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) [From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)]
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that occurred or worsened after receiving the first dose of study drug and within 6 weeks after the last dose of study drug. A TEAE may also have been a pre-treatment AE or a concurrent medical condition diagnosed before the date of first dose of study drug that increased in severity after the start of dosing.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) [From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)]
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment.
Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose [From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)]
Clinical laboratory tests included serum chemistry, hematology and urinalysis. MAV criteria:Alanine aminotransferase(U/L) >3 x upper limit of normal(ULN);albumin<2.5g/dL,<25g/L;alkaline phosphatase (U/L)>3 x ULN; aspartate aminotransferase (U/L)>3 x ULN;bicarbonate<8.0 mmol/L; bilirubin>2.0mg/dL, >34.2 μmol/L;blood urea nitrogen>30 mg/dL,>10.7mmol/L;calcium<7.0 mg/dL,<1.75 mmol/L, >11.5 mg/dL,>2.88 mmol/L;chloride<75 mmol/L,>126 mmol/L;creatine kinase(U/L) >5 xULN; creatinine>2.0 mg/dL,>177μmol/L;direct bilirubin>2 x ULN;gamma glutamyl transferase (U/L)>3 x ULN;glucose<50 mg/dL,<2.8 mmol/L,>350 mg/dL,>19.4 mmol/L;potassium<3.0 mmol/L >6.0 mmol/L; protein(g/L)<0.8 x LLN >1.2 x ULN;sodium<130mmol/L >150mmol/L;erythrocytes(10^12erythrocytes/L) <0.8 x LLN,>1.2 x ULN;hematocrit(fraction of 1)<0.8 x LLN,>1.2xULN;hemoglobin(g/L)<0.8 x LLN>1.2 x ULN;leukocytes(10^9 leukocytes/L)<0.5 x LLN >1.5 x ULN;platelets(10^9 platelets/L)<75->600. Categories with at least one participant are reported.
Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose [From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)]
Vital signs included oral body temperature measurement, supine and standing blood pressure, respiration rate, and pulse. Pulse and blood pressure was measured after 5 minutes supine and again at 1 and 3 minutes after standing. The markedly abnormal value (MAV) criteria for vital signs included systolic blood pressure < 85 mmHg, > 180 mmHg; diastolic blood pressure < 50 mmHg, > 110 mmHg; pulse < 50 beats/min, > 120 beats/min; temperature < 35.6 C > 37.7 C. Categories with data in at least one arm group are reported.
Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose [From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)]
The markedly abnormal value (MAV) criteria for 12-lead ECG parameters included ECG Mean Heart Rate < 50 beats/min, > 120 beats/min; PR Interval, Aggregate <= 80 msec, >= 200 msec; QRS Duration, Aggregate <= 80 msec, >= 180 msec; QTcB Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec); QTcF Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec). Categories with data in at least one arm group are reported.
Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose [Part 2: from first dose up to Day 66]
The markedly abnormal value (MAV) criteria for continuous 12-lead Holter ECG parameters included ECG Mean Heart Rate < 50 beats/min, > 120 beats/min; PR Interval, Aggregate <= 80 msec, >= 200 msec; QRS Duration, Aggregate <= 80 msec, >= 180 msec; QTcB Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec); QTcF Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec). Categories with data in at least one arm group are reported.
Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1] [Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose]
Part 3: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours (AUC96) for TAK-041 in RBA/Food Effect Participants [Day 1] [Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose]

Secondary Outcome Measures

Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]
Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1] [Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose]
Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]
Part 3: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in RBA/Food Effect Participants [Day 1] [Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose]
Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]
Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]
Part 3: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in RBA/Food Effect Participants [Day 1] [Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose]
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1] [Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5]
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only [Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose]
Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] [Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy Participants and Participants with Schizophrenia:

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any participant procedures including requesting that a participant fast for any laboratory evaluations.
The participant is willing to comply with study restrictions described in the protocol.
The participant is a healthy adult man or woman (of non-childbearing potential as described in the protocol)
The participant is aged 18 to 55 years, inclusive, at the time of informed consent.
The participant weighs at least 45 kilogram (kg) (99 pound [lb]) with a body mass index from 18 to 32 kilogram per square meter (kg/m^{2) for healthy participants and up
to 40.5 kg/m}2 for participants with schizophrenia, inclusive at screening.
A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception (as defined in the protocol)from signing of informed consent throughout the duration of the study and for 145 days have elapsed since the last dose of study drug.

Participants with schizophrenia only-:

Is on a stable dose of an antipsychotic medication for at least 2 months as documented by medical history and assessed by site staff.
Meets schizophrenia criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) by the Mini International Neuropsychiatric Interview (MINI).
Has Positive and Negative Syndrome Scale (PANSS) total score less than or equal to (<=) 90 and PANSS Negative Symptom Factor Score (NSFS; Sum of PANSS N1, N2, N3, N4, N6, G7, and G16) greater than or equal to (>=) 15 at screening and baseline (Day-1).
Has stable screening and baseline (Day -1) PANSS and NSFS total scores (less than [<] 20 percent (%) change).

Exclusion Criteria:

Healthy Participants:

The participant has received any investigational compound within 30 days prior to the first dose of study drug, or due to the half-life of the investigational drug is likely to still have detectable plasma levels of that compound.
The participant 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
The participant has a known hypersensitivity to any component of the formulation of TAK-041.
The participant has a positive urine/blood drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1).
The participant taken any excluded medication, supplements, or food products during the time periods listed in the protocol.
The participant is lactose intolerant (Part3 only).
If female, the participant is of childbearing potential (example, premenopausal, not sterilized).
If male, the participant intends to donate sperm during the course of this study or for 145 days have elapsed since the last dose of study drug.
The participant has evidence of current active cardiovascular, central nervous system, hepatobiliary disease including history of biliary tree disorders, gallstones, endoscopic retrograde cholangio pancreatography (ERCP), and/or cholecystectomy, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma, hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory test results (including elevated alkaline phosphatase (ALP), elevated bilirubin, elevated GGT, or elevated 5'-nucleotidase) that in the judgment of the principal investigator represents a reasonable suspicion of a disease that would contraindicate taking TAK-041, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, cholestasis, seizure disorders, and cardiac arrhythmias.
The participant 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).
Had major surgery, or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to Screening.
The participant has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1. Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody at Screening or a known history of human immunodeficiency virus (HIV) infection.
The participant has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 21 days prior to Check-in on Day -1. Cotinine test is positive at Screening or Day -1.
The participant has poor peripheral venous access.
Had a transfusion of any blood product within 30 days prior to Day 1.
Participant 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 of the principal investigator or a medically qualified sub-investigator.
The participant has a sustained resting heart rate outside the range 40 to 100 beats per minute (bpm), confirmed on repeat testing within a maximum of 30 minutes, at Screening or Check-in.
The participant has a QT interval with Fridericia correction method (QTcF) >450 millisecond (ms) or PR outside the range 120 to 220 ms, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in.
The participant has abnormal Screening or Check-in laboratory values (> upper limit of normal [ULN] for the respective serum chemistries) of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILI), ALP, gamma-glutamyl transpeptidase (GGT), 5'nucleotidase (Screening only) and/or abnormal urine osmolality, confirmed upon repeat testing.
The participant has a clinically significant history of head injury or trauma associated with loss of consciousness for >15 minutes.
Is considered by the investigator to be at an imminent risk of suicide injury to self, other, property, or participants who within the past year prior to Screening have attempted suicide. Participants having positive answer on item 4 or 5 on Columbia Suicide Severity Rating Scale (C-SSRS) (based on the past year) prior to randomization are excluded.
The participant has a history of significant skin reactions (hypersensitivity) to adhesives, metals or plastic; this criterion applies only to participants participating in the study of the two wearable digital devices.

Participants with schizophrenia only:

Has an undetectable level of baseline antipsychotic medication at Screening.
Has a lifetime diagnosis of schizoaffective disorder; a lifetime diagnosis of bipolar disorder; or a lifetime diagnosis of obsessive compulsive disorder based on the Mini International Neuropsychiatric Interview (MINI) combined with the general psychiatric evaluation. As an exception, participants with a historical prior lifetime diagnosis of schizoaffective disorder may be enrolled in the study with sponsor or designee approval provided that the principal investigator can attest that the participant's overall history and current clinical presentation and history is most consistent with schizophrenia, not schizoaffective disorder.
Has a recent (within the last 6 months) diagnosis of panic disorder, depressive episode, or other comorbid psychiatric conditions requiring clinical attention based on the MINI for DSM-5 and the general psychiatric evaluation.
Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as 4 or more alcoholic beverages per day) within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
Has a diagnosis of substance use disorder (with the exception of nicotine dependence) within the preceding 6 months based on the MINI for DSM-5 and the general psychiatric evaluation.
Has evidence or history of current clinically significant cardiovascular disease, including uncontrolled hypertension (standing or supine diastolic blood pressure >90 millimeter of mercury (mm Hg) and/or standing or supine systolic blood pressure >145 mm Hg, with or without treatment), symptomatic ischemic heart disease, uncompensated heart failure or recent (past 12 months) acute myocardial infarction or bypass surgery. Controlled essential hypertension, non-clinically significant sinus bradycardia and sinus tachycardia will not be considered significant medical illnesses and would not exclude a participant from the study. Other well-controlled medical illnesses may be permitted that do not increase hepatic risks or other safety risks to the participant's participation in the judgement of the investigator in consultation with the sponsor or designee.
Has evidence of clinically significant extrapyramidal symptoms as measured by a Simson-Angus Scale (SAS) score >6.
The participant has evidence of depression as measured by a Calgary Depression Score (CDSS) score >9.
Has received TAK-041 in a previous clinical study; or has previously or is currently participating in this study; has received treatment with other experimental therapies within the preceding 60 days or <5 half-lives prior to randomization, whichever is longer; has participated in 2 or more clinical studies within 12 months prior to Screening; or has participated in a clinical study for a psychiatric condition that is exclusionary per this protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel Early Phase Clinic Unit- Los Angeles	Glendale	California	United States	91206

Sponsors and Collaborators

Neurocrine Biosciences
Takeda

Investigators

Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Neurocrine Biosciences

ClinicalTrials.gov Identifier:

NCT02748694

Other Study ID Numbers:

TAK-041-1001
U1111-1178-6559

First Posted:

Apr 22, 2016

Last Update Posted:

Mar 19, 2021

Last Verified:

Mar 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Neurocrine Biosciences

Drug Therapy

Additional relevant MeSH terms:

Schizophrenia

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at one investigative site in the United States from 09 May 2016 to 22 September 2019.
Pre-assignment Detail	Healthy participants were enrolled in Parts 1 to 3 to receive TAK-041 or placebo in this study as a single-rising dose (SRD), multiple-rising dose (MRD) or to assess the effect of food on drug's bioavailability. Participants with stable schizophrenia received TAK-041 or placebo as an add-on therapy in Part 4.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5/20 mg	Part 1 (SRD): Cohort 2: TAK-041 10/40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the single-rising dose (SRD) period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the multiple-rising dose (MRD) period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Period Title: Overall Study
STARTED	10	6	6	6	6	6	8	6	6	6	6	9	9	8	16
COMPLETED	10	6	6	6	6	6	8	6	6	6	6	9	9	8	14
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2

Baseline Characteristics

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5/20 mg	Part 1 (SRD): Cohort 2: TAK-041 10/40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg	Total
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. Participants also received 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.	Total of all reporting groups
Overall Participants	10	6	6	6	6	6	8	6	6	6	6	9	9	8	16	114
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	40.6	36.8	29.3	44.2	42.3	40.5	35.5	39.5	38.3	37.7	42.5	35.6	34.1	45.8	44.3	39.46
Sex: Female, Male (Count of Participants)
Female	2 20%	1 16.7%	2 33.3%	2 33.3%	2 33.3%	1 16.7%	1 12.5%	2 33.3%	1 16.7%	1 16.7%	1 16.7%	2 22.2%	1 11.1%	2 25%	3 18.8%	24 21.1%
Male	8 80%	5 83.3%	4 66.7%	4 66.7%	4 66.7%	5 83.3%	7 87.5%	4 66.7%	5 83.3%	5 83.3%	5 83.3%	7 77.8%	8 88.9%	6 75%	13 81.3%	90 78.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 40%	0 0%	2 33.3%	0 0%	3 50%	2 33.3%	1 12.5%	0 0%	2 33.3%	1 16.7%	2 33.3%	2 22.2%	1 11.1%	1 12.5%	1 6.3%	22 19.3%
Not Hispanic or Latino	6 60%	6 100%	4 66.7%	6 100%	3 50%	4 66.7%	7 87.5%	6 100%	4 66.7%	5 83.3%	4 66.7%	7 77.8%	8 88.9%	7 87.5%	15 93.8%	92 80.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 33.3%	1 16.7%	0 0%	0 0%	0 0%	0 0%	1 16.7%	2 33.3%	1 16.7%	0 0%	0 0%	2 22.2%	0 0%	3 18.8%	12 10.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.9%
Black or African American	1 10%	2 33.3%	2 33.3%	3 50%	0 0%	4 66.7%	3 37.5%	2 33.3%	1 16.7%	1 16.7%	0 0%	1 11.1%	2 22.2%	5 62.5%	8 50%	35 30.7%
White	7 70%	2 33.3%	1 16.7%	3 50%	5 83.3%	2 33.3%	5 62.5%	2 33.3%	3 50%	4 66.7%	5 83.3%	8 88.9%	4 44.4%	3 37.5%	5 31.3%	59 51.8%
More than one race	2 20%	0 0%	1 16.7%	0 0%	1 16.7%	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 16.7%	0 0%	1 11.1%	0 0%	0 0%	7 6.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	6 100%	6 100%	6 100%	6 100%	6 100%	8 100%	6 100%	6 100%	6 100%	6 100%	9 100%	9 100%	8 100%	16 100%	114 100%
Height (cm) [Mean (Full Range) ]
Mean (Full Range) [cm]	176.9	174.3	171.2	175.2	164.8	178.3	178.3	174.2	168.3	173.8	173.0	175.3	175.7	173.9	174.9	174.24
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	79.68	78.63	74.43	86.97	68.52	89.83	81.79	83.40	77.20	78.22	76.43	76.07	79.42	91.46	98.58	81.82
Body Mass Index (BMI) (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	25.47	25.91	25.43	28.36	25.28	28.22	25.80	27.63	27.14	25.74	25.44	24.76	25.68	30.31	32.05	27.24

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
Description	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that occurred or worsened after receiving the first dose of study drug and within 6 weeks after the last dose of study drug. A TEAE may also have been a pre-treatment AE or a concurrent medical condition diagnosed before the date of first dose of study drug that increased in severity after the start of dosing.
Time Frame	From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)

Outcome Measure Data

Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	10	6	6	6	6	6	6	6	8	6	6	6	6	9	9	8	16
Number [percentage of participants]	40.0 400%	0 0%	0 0%	0 0%	0 0%	33.3 555%	33.3 416.3%	33.3 555%	37.5 625%	66.7 1111.7%	66.7 1111.7%	50.0 555.6%	83.3 925.6%	11.1 138.8%	22.2 138.8%	75.0 65.8%	56.3 NaN

2. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Description	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug or due to a study procedure; it did not necessarily have to have a causal relationship with this treatment.
Time Frame	From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)

Outcome Measure Data

Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	10	6	6	6	6	6	6	6	8	6	6	6	6	9	9	8	16
Number [percentage of participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN

3. Primary Outcome

Title	Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose
Description	Clinical laboratory tests included serum chemistry, hematology and urinalysis. MAV criteria:Alanine aminotransferase(U/L) >3 x upper limit of normal(ULN);albumin<2.5g/dL,<25g/L;alkaline phosphatase (U/L)>3 x ULN; aspartate aminotransferase (U/L)>3 x ULN;bicarbonate<8.0 mmol/L; bilirubin>2.0mg/dL, >34.2 μmol/L;blood urea nitrogen>30 mg/dL,>10.7mmol/L;calcium<7.0 mg/dL,<1.75 mmol/L, >11.5 mg/dL,>2.88 mmol/L;chloride<75 mmol/L,>126 mmol/L;creatine kinase(U/L) >5 xULN; creatinine>2.0 mg/dL,>177μmol/L;direct bilirubin>2 x ULN;gamma glutamyl transferase (U/L)>3 x ULN;glucose<50 mg/dL,<2.8 mmol/L,>350 mg/dL,>19.4 mmol/L;potassium<3.0 mmol/L >6.0 mmol/L; protein(g/L)<0.8 x LLN >1.2 x ULN;sodium<130mmol/L >150mmol/L;erythrocytes(10^12erythrocytes/L) <0.8 x LLN,>1.2 x ULN;hematocrit(fraction of 1)<0.8 x LLN,>1.2xULN;hemoglobin(g/L)<0.8 x LLN>1.2 x ULN;leukocytes(10^9 leukocytes/L)<0.5 x LLN >1.5 x ULN;platelets(10^9 platelets/L)<75->600. Categories with at least one participant are reported.
Time Frame	From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)

Outcome Measure Data

Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	10	6	6	6	6	6	6	6	8	6	6	6	6	9	9	8	16
Creatine Kinase, > 5 x ULN	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 278.3%	12.5 208.3%	0 0%	0 0%	0 0%	0 0%	0 0%	11.1 69.4%	0 0%	12.5 NaN
Glucose < 50 mg/dL, < 2.8 mmol/L	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 208.8%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
Aspartate Aminotransferase, > 3 x ULN	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	11.1 69.4%	0 0%	6.3 NaN
Leukocytes, > 1.5 x ULN	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6.3 NaN
Platelets, > 600 10^9 platelets/L	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6.3 NaN

4. Primary Outcome

Title	Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Description	Vital signs included oral body temperature measurement, supine and standing blood pressure, respiration rate, and pulse. Pulse and blood pressure was measured after 5 minutes supine and again at 1 and 3 minutes after standing. The markedly abnormal value (MAV) criteria for vital signs included systolic blood pressure < 85 mmHg, > 180 mmHg; diastolic blood pressure < 50 mmHg, > 110 mmHg; pulse < 50 beats/min, > 120 beats/min; temperature < 35.6 C > 37.7 C. Categories with data in at least one arm group are reported.
Time Frame	From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)

Outcome Measure Data

Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	10	6	6	6	6	6	6	6	8	6	6	6	6	9	9	8	16
Systolic Blood Pressure, Standing, < 85 mmHg	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	12.5 11%	0 NaN
Systolic Blood Pressure, Supine, < 85 mmHg	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
Systolic Blood Pressure, 5 min Supine, < 85 mmHg	10.0 100%	0 0%	0 0%	0 0%	16.7 278.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	12.5 11%	6.3 NaN
Systolic Blood Pressure, 1 min Standing, < 85 mmHg	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 185.6%	0 0%	0 0%	12.5 11%	0 NaN
Systolic Blood Pressure, 3 min Standing, < 85 mmHg	10.0 100%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	12.5 11%	0 NaN
Diastolic Blood Pressure, 5 min Supine, < 50 mmHg	10.0 100%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 278.3%	0 0%	0 0%	0 0%	11.1 69.4%	0 0%	0 NaN
Diastolic Blood Pressure,1 min Standing,>110 mmHg	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6.3 NaN
Diastolic Blood Pressure,3 min Standing,>110 mmHg	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	12.5 11%	6.3 NaN
Pulse Rate, Standing, < 50 beats/min	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 185.6%	0 0%	0 0%	0 0%	0 0%	0 NaN
Pulse Rate, Standing, > 120 beats/min	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 278.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6.3 NaN
Pulse Rate, Supine, < 50 beats/min	10.0 100%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 185.6%	0 0%	0 0%	0 0%	12.5 11%	0 NaN
Pulse Rate, 5 min Supine, < 50 beats/min	50.0 500%	16.7 278.3%	33.3 555%	33.3 555%	33.3 555%	16.7 278.3%	33.3 416.3%	50.0 833.3%	62.5 1041.7%	33.3 555%	16.7 278.3%	83.3 925.6%	33.3 370%	0 0%	33.3 208.1%	12.5 11%	12.5 NaN
Pulse Rate, 1 min Standing, < 50 beats/min	10.0 100%	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 208.8%	0 0%	0 0%	0 0%	0 0%	33.3 370%	16.7 185.6%	0 0%	0 0%	0 0%	0 NaN
Pulse Rate, 1 min Standing, > 120 beats/min	0 0%	0 0%	0 0%	0 0%	16.7 278.3%	0 0%	16.7 208.8%	0 0%	0 0%	0 0%	33.3 555%	0 0%	0 0%	0 0%	0 0%	25.0 21.9%	12.5 NaN
Pulse Rate, 3 min Standing, < 50 beats/min	10.0 100%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	33.3 370%	0 0%	0 0%	0 0%	0 0%	0 NaN
Pulse Rate, 3 min Standing, > 120 beats/min	0 0%	16.7 278.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	33.3 555%	0 0%	0 0%	0 0%	0 0%	0 0%	25.0 21.9%	12.5 NaN
Temperature, < 35.6 C	20.0 200%	0 0%	0 0%	0 0%	0 0%	33.3 555%	16.7 208.8%	33.3 555%	37.5 625%	33.3 555%	16.7 278.3%	16.7 185.6%	33.3 370%	11.1 138.8%	0 0%	25.0 21.9%	31.3 NaN

5. Primary Outcome

Title	Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose
Description	The markedly abnormal value (MAV) criteria for 12-lead ECG parameters included ECG Mean Heart Rate < 50 beats/min, > 120 beats/min; PR Interval, Aggregate <= 80 msec, >= 200 msec; QRS Duration, Aggregate <= 80 msec, >= 180 msec; QTcB Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec); QTcF Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec). Categories with data in at least one arm group are reported.
Time Frame	From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)

Outcome Measure Data

Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part 4: MRD: Placebo	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	10	6	6	6	6	6	6	6	8	6	6	6	6	9	9	8	16
ECG Mean Heart Rate, < 50 beats/min	20.0 200%	16.7 278.3%	33.3 555%	50.0 833.3%	33.3 555%	0 0%	16.7 208.8%	50.0 833.3%	37.5 625%	16.7 278.3%	16.7 278.3%	66.7 741.1%	33.3 370%	0 0%	22.2 138.8%	12.5 11%	12.5 NaN
PR Interval, Aggregate, >= 200 msec	0 0%	33.3 555%	33.3 555%	33.3 555%	33.3 555%	16.7 278.3%	16.7 208.8%	0 0%	25.0 416.7%	0 0%	0 0%	0 0%	0 0%	0 0%	11.1 69.4%	12.5 11%	12.5 NaN
QTcB Interval, Aggregate, >= 500 msec	10.0 100%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	6.3 NaN
QTcF Interval, Aggregate, >= 500 msec	0 0%	0 0%	0 0%	0 0%	0 0%	16.7 278.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
QRS Duration, Aggregate, <= 80 msec	20.0 200%	33.3 555%	50.0 833.3%	33.3 555%	50.0 833.3%	33.3 555%	33.3 416.3%	16.7 278.3%	0 0%	33.3 555%	33.3 555%	66.7 741.1%	16.7 185.6%	33.3 416.3%	11.1 69.4%	75.0 65.8%	31.3 NaN

6. Primary Outcome

Title	Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose
Description	The markedly abnormal value (MAV) criteria for continuous 12-lead Holter ECG parameters included ECG Mean Heart Rate < 50 beats/min, > 120 beats/min; PR Interval, Aggregate <= 80 msec, >= 200 msec; QRS Duration, Aggregate <= 80 msec, >= 180 msec; QTcB Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec); QTcF Interval, Aggregate <= 300 msec, >= 500 msec OR (>= 30 msec change from baseline and >= 450 msec). Categories with data in at least one arm group are reported.
Time Frame	Part 2: from first dose up to Day 66

Outcome Measure Data

Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug. Continuous 12-lead Holter ECG monitoring was performed in Part 2 only.

Arm/Group Title	Part 2 (MRD): Placebo Cohorts 1-4	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.
Measure Participants	8	6	6	6	6
ECG Mean Heart Rate, < 50 beats/min	0 0%	0 0%	0 0%	50.0 833.3%	16.7 278.3%
PR Interval, Aggregate, >= 200 msec	25.0 250%	0 0%	0 0%	0 0%	0 0%
QRS Duration, Aggregate, <= 80 msec	0 0%	0 0%	16.7 278.3%	0 0%	0 0%

7. Primary Outcome

Title	Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1]
Description
Time Frame	Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Data for Regimen C were combined from Part 1 Cohort 2 and Part 2 Cohort 1 (Day 1) to report RBA/food effect on suspension formulation.

Arm/Group Title	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part3:RBA/Food Effect:Regimen C-Part 1 Cohort2,Part 2 Cohort 1
Arm/Group Description	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	Regimen C included participants from Part 1 Cohort 2 and Part 2 Cohort 1 who received TAK-041, 40 mg suspension, orally on Day 1 in fasted condition.
Measure Participants	9	9	12
Mean (Standard Deviation) [ng/mL]	715.4 (192.54)	838.3 (176.04)	648.4 (158.67)

8. Primary Outcome

Title	Part 3: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours (AUC96) for TAK-041 in RBA/Food Effect Participants [Day 1]
Description
Time Frame	Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Data for Regimen C were combined from Part 1 Cohort 2 and Part 2 Cohort 1 (Day 1) to report RBA/food effect on suspension formulation.

Arm/Group Title	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part3:RBA/Food Effect:Regimen C-Part 1 Cohort2,Part 2 Cohort 1
Arm/Group Description	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	Regimen C included participants from Part 1 Cohort 2 and Part 2 Cohort 1 who received TAK-041, 40 mg suspension, orally on Day 1 in fasted condition.
Measure Participants	9	9	12
Mean (Standard Deviation) [h*ng/mL]	41564.5 (7713.08)	45499.1 (16007.58)	37795.2 (5667.55)

9. Secondary Outcome

Title	Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [ng/mL]	139.8 (15.25)	193.3 (27.75)	909.5 (225.29)	1200.0 (147.38)	1121.7 (175.31)

10. Secondary Outcome

Title	Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	6	6
Mean (Standard Deviation) [ng/mL]	450.5 (90.25)	747.2 (103.22)

11. Secondary Outcome

Title	Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	15
Mean (Standard Deviation) [ng/mL]	549.7 (146.05)	879.7 (217.95)	1260.8 (265.22)	1760.0 (349.69)	1266.5 (366.10)

12. Secondary Outcome

Title	Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	6	6	6	6	6
Median (Full Range) [hours]	0.992	1.742	3.000	13.017	13.517

13. Secondary Outcome

Title	Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	6	6
Median (Full Range) [hours]	1.992	1.583

14. Secondary Outcome

Title	Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	15
Median (Full Range) [hours]	2.517	1.525	2.500	3.000	2.000

15. Secondary Outcome

Title	Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1]
Description
Time Frame	Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Data for Regimen C were combined from Part 1 Cohort 2 and Part 2 Cohort 1 (Day 1) to report RBA/food effect on suspension formulation.

Arm/Group Title	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part3:RBA/Food Effect:Regimen C-Part 1 Cohort2,Part 2 Cohort 1
Arm/Group Description	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	Regimen C included participants from Part 1 Cohort 2 and Part 2 Cohort 1 who received TAK-041, 40 mg suspension, orally on Day 1 in fasted condition.
Measure Participants	9	9	12
Median (Full Range) [hours]	2.000	2.000	1.817

16. Secondary Outcome

Title	Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [h*ng/mL]	1662.3 (390.74)	2844.6 (263.78)	15594.9 (5560.51)	22471.2 (4340.25)	21426.6 (6026.07)

17. Secondary Outcome

Title	Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	6	6
Mean (Standard Deviation) [h*ng/mL]	6399.5 (1809.44)	11955.2 (1091.59)

18. Secondary Outcome

Title	Parts 2 and 4: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	15
Mean (Standard Deviation) [h*ng/mL]	9188.0 (3095.87)	14556.7 (4317.73)	22450.3 (3625.16)	28014.6 (7698.01)	20400.8 (5096.46)

19. Secondary Outcome

Title	Part 3: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in RBA/Food Effect Participants [Day 1]
Description
Time Frame	Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Data for Regimen C were combined from Part 1 Cohort 2 and Part 2 Cohort 1 (Day 1) to report RBA/food effect on suspension formulation.

Arm/Group Title	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part3:RBA/Food Effect:Regimen C-Part 1 Cohort2,Part 2 Cohort 1
Arm/Group Description	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	Regimen C included participants from Part 1 Cohort 2 and Part 2 Cohort 1 who received TAK-041, 40 mg suspension, orally on Day 1 in fasted condition.
Measure Participants	9	9	12
Mean (Standard Deviation) [h*ng/mL]	11940.8 (3052.59)	13827.9 (5143.36)	10571.6 (2643.23)

20. Secondary Outcome

Title	Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [h*ng/mL]	5237.2 (1107.97)	9746.9 (781.89)	59514.3 (14414.25)	92784.6 (13410.06)	90585.1 (15742.96)

21. Secondary Outcome

Title	Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	6	6
Mean (Standard Deviation) [h*ng/mL]	21180.0 (5680.75)	40487.8 (3088.81)

22. Secondary Outcome

Title	Parts 2 and 4: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	15
Mean (Standard Deviation) [h*ng/mL]	35102.6 (6612.50)	60770.4 (15609.67)	91712.9 (12328.54)	123645.0 (29616.79)	90372.3 (22678.03)

23. Secondary Outcome

Title	Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [h*ng/mL]	18038.1 (9735.91)	44649.4 (5067.39)	251124.1 (67210.68)	344075.1 (145462.41)	361251.2 (97096.24)

24. Secondary Outcome

Title	Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	6	6
Mean (Standard Deviation) [h*ng/mL]	104692.7 (48397.26)	202185.0 (38724.05)

25. Secondary Outcome

Title	Parts 2 and 4: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	15
Mean (Standard Deviation) [h*ng/mL]	55530.5 (7016.30)	99401.9 (25287.60)	147300.0 (16846.42)	203506.2 (49784.48)	148889.0 (40389.92)

26. Secondary Outcome

Title	Part 3: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in RBA/Food Effect Participants [Day 1]
Description
Time Frame	Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Data for Regimen C were combined from Part 1 Cohort 2 and Part 2 Cohort 1 (Day 1) to report RBA/food effect on suspension formulation.

Arm/Group Title	Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A	Part 3: RBA/Food Effect: Regimen B	Part3:RBA/Food Effect:Regimen C-Part 1 Cohort2,Part 2 Cohort 1
Arm/Group Description	TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.	TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.	Regimen C included participants from Part 1 Cohort 2 and Part 2 Cohort 1 who received TAK-041, 40 mg suspension, orally on Day 1 in fasted condition.
Measure Participants	9	9	12
Mean (Standard Deviation) [h*ng/mL]	116064.6 (36590.93)	126001.0 (34652.19)	128857.7 (81053.57)

27. Secondary Outcome

Title	Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. For Part 1 (SRD): Cohorts 1 and 2: TAK-041 5 and 10 mg respectively data could not be analyzed as follow-up time was not enough to calculate AUC0-inf because of the long half-life of TAK-041.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	0	0	6	6	6
Mean (Standard Deviation) [h*ng/mL]	283461.1 (96704.07)	381403.3 (208693.96)	395932.4 (129676.19)

28. Secondary Outcome

Title	Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	4	6
Mean (Standard Deviation) [h*ng/mL]	122801.1 (40764.68)	203288.4 (39395.16)

29. Secondary Outcome

Title	Parts 2 and 4: AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	15
Mean (Standard Deviation) [h*ng/mL]	55530.5 (7016.30)	99401.9 (25287.60)	147300.0 (16846.42)	203506.2 (49784.48)	148889.0 (40389.92)

30. Secondary Outcome

Title	Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1]
Description
Time Frame	Part 1: Day 1 pre-dose and at multiple time points post dose, up to 96 hours for Cohorts 1 and 2; up to 168 hours for Cohorts 3-5

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. For Part 1 (SRD): Cohorts 1 and 2: TAK-041 5 and 10 mg respectively data could not be analyzed as follow-up time was not enough to calculate T1/2z because of the long half-life of TAK-041.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 5 mg	Part 1 (SRD): Cohort 2: TAK-041 10 mg	Part 1 (SRD): Cohort 3: TAK-041 80 mg	Part 1 (SRD): Cohort 4: TAK-041 120 mg	Part 1 (SRD): Cohort 5: TAK-041 160 mg
Arm/Group Description	TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.	TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.
Measure Participants	0	0	6	6	6
Median (Full Range) [hours]	284.0	208.0	260.6

31. Secondary Outcome

Title	Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only
Description
Time Frame	Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 1 (SRD): Cohort 1: TAK-041 20 mg	Part 1 (SRD): Cohort 2: TAK-041 40 mg
Arm/Group Description	TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.	TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.
Measure Participants	4	6
Median (Full Range) [hours]	312.4	306.3

32. Secondary Outcome

Title	Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1]
Description
Time Frame	Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Outcome Measure Data

Analysis Population Description
PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Part 2 (MRD): Cohort 1: TAK-041 40/20 mg	Part 2 (MRD): Cohort 2: TAK-041 80/40 mg	Part 2 (MRD): Cohort 3: TAK-041 120/60 mg	Part 2 (MRD): Cohort 4: TAK-041 160/80 mg	Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.	TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
Measure Participants	6	6	6	6	13
Median (Full Range) [hours]	196.2	313.1	153.5	263.0	300.1

Adverse Events

	Part 1 (SRD): Placebo Cohorts 1-5		Part 1 (SRD): Cohort 1: TAK-041 5 mg		Part 1 (SRD): Cohort 2: TAK-041 10 mg		Part 1 (SRD): Cohort 1: TAK-041 20 mg		Part 1 (SRD): Cohort 2: TAK-041 40 mg		Part 1 (SRD): Cohort 3: TAK-041 80 mg		Part 1 (SRD): Cohort 4: TAK-041 120 mg		Part 1 (SRD): Cohort 5: TAK-041 160 mg		Part 2 (MRD): Placebo Cohorts 1-4		Part 2 (MRD): Cohort 1: TAK-041 40/20 mg		Part 2 (MRD): Cohort 2: TAK-041 80/40 mg		Part 2 (MRD): Cohort 3: TAK-041 120/60 mg		Part 2 (MRD): Cohort 4: TAK-041 160/80 mg		Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A		Part 3: RBA/Food Effect: Regimen B		Part 4: MRD: Placebo		Part 4: MRD: TAK-041 160/80 mg
Time Frame	From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Arm/Group Title	Part 1 (SRD): Placebo Cohorts 1-5		Part 1 (SRD): Cohort 1: TAK-041 5 mg		Part 1 (SRD): Cohort 2: TAK-041 10 mg		Part 1 (SRD): Cohort 1: TAK-041 20 mg		Part 1 (SRD): Cohort 2: TAK-041 40 mg		Part 1 (SRD): Cohort 3: TAK-041 80 mg		Part 1 (SRD): Cohort 4: TAK-041 120 mg		Part 1 (SRD): Cohort 5: TAK-041 160 mg		Part 2 (MRD): Placebo Cohorts 1-4		Part 2 (MRD): Cohort 1: TAK-041 40/20 mg		Part 2 (MRD): Cohort 2: TAK-041 80/40 mg		Part 2 (MRD): Cohort 3: TAK-041 120/60 mg		Part 2 (MRD): Cohort 4: TAK-041 160/80 mg		Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A		Part 3: RBA/Food Effect: Regimen B		Part 4: MRD: Placebo		Part 4: MRD: TAK-041 160/80 mg
Arm/Group Description	TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.		TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.		TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.		TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period.		TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period.		TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.		TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.		TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period.		TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period.		TAK-041 40 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 20 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.		TAK-041 80 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 40 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.		TAK-041 120 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 60 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.		TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 in fasted healthy participants followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in the MRD period.		TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1.		TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2.		TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia		TAK-041 160 mg as loading dose, suspension, orally, once on Day 1 followed by 80 mg (half the initial dose) as a maintenance dose on Days 8, 15 and 22 in participants with schizophrenia.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Serious Adverse Events
	Part 1 (SRD): Placebo Cohorts 1-5		Part 1 (SRD): Cohort 1: TAK-041 5 mg		Part 1 (SRD): Cohort 2: TAK-041 10 mg		Part 1 (SRD): Cohort 1: TAK-041 20 mg		Part 1 (SRD): Cohort 2: TAK-041 40 mg		Part 1 (SRD): Cohort 3: TAK-041 80 mg		Part 1 (SRD): Cohort 4: TAK-041 120 mg		Part 1 (SRD): Cohort 5: TAK-041 160 mg		Part 2 (MRD): Placebo Cohorts 1-4		Part 2 (MRD): Cohort 1: TAK-041 40/20 mg		Part 2 (MRD): Cohort 2: TAK-041 80/40 mg		Part 2 (MRD): Cohort 3: TAK-041 120/60 mg		Part 2 (MRD): Cohort 4: TAK-041 160/80 mg		Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A		Part 3: RBA/Food Effect: Regimen B		Part 4: MRD: Placebo		Part 4: MRD: TAK-041 160/80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Part 1 (SRD): Placebo Cohorts 1-5		Part 1 (SRD): Cohort 1: TAK-041 5 mg		Part 1 (SRD): Cohort 2: TAK-041 10 mg		Part 1 (SRD): Cohort 1: TAK-041 20 mg		Part 1 (SRD): Cohort 2: TAK-041 40 mg		Part 1 (SRD): Cohort 3: TAK-041 80 mg		Part 1 (SRD): Cohort 4: TAK-041 120 mg		Part 1 (SRD): Cohort 5: TAK-041 160 mg		Part 2 (MRD): Placebo Cohorts 1-4		Part 2 (MRD): Cohort 1: TAK-041 40/20 mg		Part 2 (MRD): Cohort 2: TAK-041 80/40 mg		Part 2 (MRD): Cohort 3: TAK-041 120/60 mg		Part 2 (MRD): Cohort 4: TAK-041 160/80 mg		Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A		Part 3: RBA/Food Effect: Regimen B		Part 4: MRD: Placebo		Part 4: MRD: TAK-041 160/80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		2/6 (33.3%)		2/6 (33.3%)		3/8 (37.5%)		4/6 (66.7%)		4/6 (66.7%)		3/6 (50%)		5/6 (83.3%)		1/9 (11.1%)		2/9 (22.2%)		6/8 (75%)		9/16 (56.3%)
Cardiac disorders
Palpitations	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Eye disorders
Eyelid oedema	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Gastrointestinal disorders
Diarrhoea	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Abdominal pain upper	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		1/9 (11.1%)		0/8 (0%)		0/16 (0%)
Nausea	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/9 (11.1%)		2/8 (25%)		0/16 (0%)
Abdominal discomfort	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/16 (0%)
Aphthous ulcer	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		1/16 (6.3%)
Toothache	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/16 (0%)
General disorders
Application site dermatitis	1/10 (10%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Catheter site phlebitis	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Fatigue	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Feeling abnormal	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Energy increased	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		1/16 (6.3%)
Application site irritation	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Infections and infestations
Upper respiratory tract infection	2/10 (20%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Gastroenteritis	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Conjunctivitis	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Thermal burn	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Arthropod bite	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Contusion	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/9 (11.1%)		1/9 (11.1%)		0/8 (0%)		0/16 (0%)
Limb fracture	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Road traffic accident	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Skin abrasion	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Investigations
Blood creatine phosphokinase increased	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Myalgia	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Nervous system disorders
Headache	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		1/8 (12.5%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		3/6 (50%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		2/16 (12.5%)
Dizziness	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Paraesthesia	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Somnolence	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		4/16 (25%)
Syncope	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		1/9 (11.1%)		0/8 (0%)		0/16 (0%)
Speech disorder	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		1/16 (6.3%)
Psychiatric disorders
Agitation	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/16 (0%)
Abnormal dreams	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		2/8 (25%)		2/16 (12.5%)
Change in sustained attention	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		2/16 (12.5%)
Euphoric mood	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Throat irritation	1/10 (10%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Nasal congestion	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Rhinorrhoea	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Cough	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Rash	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		0/16 (0%)
Dermatitis contact	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		0/8 (0%)		1/16 (6.3%)
Vascular disorders
Orthostatic hypotension	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/9 (0%)		1/8 (12.5%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.

Results Point of Contact

Name/Title	Medical Director
Organization	Takeda
Phone	+1-877-825-3327
Email	trialdisclosures@takeda.com

Responsible Party:

Neurocrine Biosciences

ClinicalTrials.gov Identifier:

NCT02748694

Other Study ID Numbers:

TAK-041-1001
U1111-1178-6559

First Posted:

Apr 22, 2016

Last Update Posted:

Mar 19, 2021

Last Verified:

Mar 1, 2021

Phase 1 TAK-041 First-in-Human Safety, Tolerability, and Pharmacokinetics Study

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Healthy Participants and Participants with Schizophrenia:

Participants with schizophrenia only-:

Exclusion Criteria:

Healthy Participants:

Participants with schizophrenia only:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact