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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1178-6559 | Registry Identifier | WHO |
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| Name | Class |
|---|---|
| Takeda | INDUSTRY |
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TAK-041:
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:
Part 2 consists of 4 cohorts, participants will be randomly assigned to one of the two treatments:
Part 3 consists of 2 cohorts, participants will be randomly assigned to one of the two treatments under fasted state or fed state:
Part 4 consists of 1 cohort, participants will be randomly assigned to one of the two treatments:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Placebo Comparator | TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
|
| Part 1 (SRD): Cohort 1: TAK-041 5/20 mg | Experimental | 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. |
|
| Part 1 (SRD): Cohort 2: TAK-041 10/40 mg | Experimental | 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. |
|
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Experimental | TAK-041 80 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
|
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Experimental | TAK-041 120 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-041 | Drug | TAK-041 tablets or oral suspension. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 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. | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 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. | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
| Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Healthy Participants and Participants with Schizophrenia:
Participants with schizophrenia only-:
Exclusion Criteria:
Healthy Participants:
Participants with schizophrenia only:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel Early Phase Clinic Unit- Los Angeles | Glendale | California | 91206 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35277995 | Derived | Yin W, Han D, Khudyakov P, Behrje R, Posener J, Laurenza A, Arkilo D. A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy participants and patients with stable schizophrenia. Br J Clin Pharmacol. 2022 Aug;88(8):3872-3882. doi: 10.1111/bcp.15305. Epub 2022 Apr 17. |
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Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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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.
Participants took part in the study at one investigative site in the United States from 09 May 2016 to 22 September 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 (SRD): Placebo Cohorts 1-5 | TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the single-rising dose (SRD) period. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| FG007 | 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. |
| FG008 | 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. |
| FG009 | 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. |
| FG010 | 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. |
| FG011 | 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. |
| FG012 | 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. |
| FG013 | Part 4: MRD: Placebo | TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia |
| FG014 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Part 1 (SRD): Cohort 1: TAK-041 5/20 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 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. | Safety Set included all participants who were enrolled and received at least 1 dose of study drug. | Posted | Number | percentage of participants | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
|
From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site dermatitis | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 27, 2019 | Feb 9, 2021 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jul 3, 2018 | Feb 9, 2021 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000721087 | TAK-041 |
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| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Experimental | TAK-041 160 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
|
| Part 2 (MRD): Placebo Cohorts 1-4 | Placebo Comparator | TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the multiple-rising dose (MRD) period. |
|
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Experimental | 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. |
|
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Experimental | 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. |
|
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Experimental | 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. |
|
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Experimental | 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. |
|
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Experimental | TAK-041 40 mg, tablet, orally, once on Day 1 in fasted state (Regimen A) in Cohort 1. |
|
| Part 3: RBA/Food Effect: Regimen B | Experimental | TAK-041 40 mg, tablet, orally, once on Day 1 in fed state (Regimen B) in Cohort 2. |
|
| Part 4: MRD: Placebo | Placebo Comparator | TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia |
|
| Part 4: MRD: TAK-041 160/80 mg | Experimental | 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. |
|
| TAK-041 Placebo | Drug | TAK-041 placebo-matching suspension or tablet. |
|
| From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
| Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | 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. | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
| Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | 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. | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
| Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | 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 2: from first dose up to Day 66 |
| 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 |
| 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 |
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.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | Part 2 (MRD): Placebo Cohorts 1-4 | TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period. |
| BG007 | 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. |
| BG008 | 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. |
| BG009 | 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. |
| BG010 | 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. |
| BG011 | 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. |
| BG012 | 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. |
| BG013 | Part 4: MRD: Placebo | TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia |
| BG014 | 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. |
| BG015 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Height | Mean | Full Range | cm |
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| Weight | Mean | Full Range | kg |
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| Body Mass Index (BMI) | BMI = Weight(kg)/height(m)^2. | Mean | Full Range | kg/m^2 |
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TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
| OG001 | Part 1 (SRD): Cohort 1: TAK-041 5 mg | TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
| OG002 | Part 1 (SRD): Cohort 2: TAK-041 10 mg | TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. |
| OG003 | Part 1 (SRD): Cohort 1: TAK-041 20 mg | TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period. |
| OG004 | Part 1 (SRD): Cohort 2: TAK-041 40 mg | TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | Part 2 (MRD): Placebo Cohorts 1-4 | TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
| OG013 | 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. |
| OG014 | 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. |
| OG015 | Part 4: MRD: Placebo | TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia |
| OG016 | 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. |
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| Primary | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 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. | Safety Set included all participants who were enrolled and received at least 1 dose of study drug. | Posted | Number | percentage of participants | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
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| Primary | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | 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. | Safety Set included all participants who were enrolled and received at least 1 dose of study drug. | Posted | Number | percentage of participants | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
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| Primary | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | 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. | Safety Set included all participants who were enrolled and received at least 1 dose of study drug. | Posted | Number | percentage of participants | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
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| Primary | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | 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. | Safety Set included all participants who were enrolled and received at least 1 dose of study drug. | Posted | Number | percentage of participants | From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks) |
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| Primary | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | 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. | 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. | Posted | Number | percentage of participants | Part 2: from first dose up to Day 66 |
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| Primary | Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1] | 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. | Posted | Mean | Standard Deviation | ng/mL | Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose |
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| Primary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose |
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| Secondary | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| Secondary | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | ng/mL | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] | 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. | Posted | Mean | Standard Deviation | ng/mL | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| Secondary | Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Median | Full Range | hours | 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 |
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| Secondary | 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 | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Median | Full Range | hours | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] | 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. | Posted | Median | Full Range | hours | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| Secondary | Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1] | 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. | Posted | Median | Full Range | hours | Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose |
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| Secondary | Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | h*ng/mL | 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 |
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| Secondary | 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 | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | h*ng/mL | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| Secondary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose |
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| Secondary | Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | h*ng/mL | 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 |
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| Secondary | 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 | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | h*ng/mL | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| Secondary | Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | h*ng/mL | 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 |
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| Secondary | 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 | PK Set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in the urine. | Posted | Mean | Standard Deviation | h*ng/mL | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| Secondary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose |
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| Secondary | Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | 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 |
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| Secondary | 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 | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | 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] | 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. | Posted | Mean | Standard Deviation | h*ng/mL | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| Secondary | Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1] | 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. | Posted | Median | Full Range | hours | 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 |
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| Secondary | 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 | 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. | Posted | Median | Full Range | hours | Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose |
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| Secondary | Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] | 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. | Posted | Median | Full Range | hours | Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose |
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| 0 |
| 10 |
| 0 |
| 10 |
| 4 |
| 10 |
| EG001 | Part 1 (SRD): Cohort 1: TAK-041 5 mg | TAK-041 5 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Part 1 (SRD): Cohort 2: TAK-041 10 mg | TAK-041 10 mg, suspension, orally, once on Day 1 in fasted healthy participants in the SRD period. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | Part 1 (SRD): Cohort 1: TAK-041 20 mg | TAK-041 20 mg, suspension, orally, once on Day 8 in the SRD period. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG004 | Part 1 (SRD): Cohort 2: TAK-041 40 mg | TAK-041 40 mg, suspension, orally, once on Day 8 in the SRD period. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG005 | 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. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | 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. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG007 | 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. | 0 | 6 | 0 | 8 | 2 | 6 |
| EG008 | Part 2 (MRD): Placebo Cohorts 1-4 | TAK-041 placebo-matching suspension, orally, once on Day 1 in fasted healthy participants in the MRD period. | 0 | 8 | 0 | 6 | 3 | 8 |
| EG009 | 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. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG010 | 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. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG011 | 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. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG012 | 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. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG013 | 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. | 0 | 9 | 0 | 9 | 1 | 9 |
| EG014 | 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. | 0 | 9 | 0 | 9 | 2 | 9 |
| EG015 | Part 4: MRD: Placebo | TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia | 0 | 8 | 0 | 8 | 6 | 8 |
| EG016 | 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. | 0 | 16 | 0 | 16 | 9 | 16 |
| Catheter site phlebitis | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Feeling abnormal | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Energy increased | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Limb fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Speech disorder | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
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| Eyelid oedema | Eye disorders | MedDRA 21.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
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| Application site irritation | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Abnormal dreams | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Change in sustained attention | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Euphoric mood | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
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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.
| Glucose < 50 mg/dL, < 2.8 mmol/L |
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| Aspartate Aminotransferase, > 3 x ULN |
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| Leukocytes, > 1.5 x ULN |
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| Platelets, > 600 10^9 platelets/L |
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| Systolic Blood Pressure, Supine, < 85 mmHg |
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| Systolic Blood Pressure, 5 min Supine, < 85 mmHg |
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| Systolic Blood Pressure, 1 min Standing, < 85 mmHg |
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| Systolic Blood Pressure, 3 min Standing, < 85 mmHg |
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| Diastolic Blood Pressure, 5 min Supine, < 50 mmHg |
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| Diastolic Blood Pressure,1 min Standing,>110 mmHg |
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| Diastolic Blood Pressure,3 min Standing,>110 mmHg |
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| Pulse Rate, Standing, < 50 beats/min |
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| Pulse Rate, Standing, > 120 beats/min |
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| Pulse Rate, Supine, < 50 beats/min |
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| Pulse Rate, 5 min Supine, < 50 beats/min |
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| Pulse Rate, 1 min Standing, < 50 beats/min |
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| Pulse Rate, 1 min Standing, > 120 beats/min |
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| Pulse Rate, 3 min Standing, < 50 beats/min |
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| Pulse Rate, 3 min Standing, > 120 beats/min |
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| Temperature, < 35.6 C |
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| PR Interval, Aggregate, >= 200 msec |
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| QTcB Interval, Aggregate, >= 500 msec |
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| QTcF Interval, Aggregate, >= 500 msec |
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| QRS Duration, Aggregate, <= 80 msec |
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| PR Interval, Aggregate, >= 200 msec |
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| QRS Duration, Aggregate, <= 80 msec |
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