Healthy Volunteers, Schizophrenia
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of TAK-041: 1. Following oral single and multiple doses in healthy participants. 2. As add-on therapy to antipsychotics in stable schizophrenia participants. 3. To determine the oral bioavailability of the TAK-041 tablet formulation compared to the oral suspension formulation in the fasted state. 4. To assess the effect of food on the PK of TAK-041 in healthy participants.
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.
Interventions
DRUGTAK-041
TAK-041 tablets or oral suspension.
DRUGTAK-041 Placebo
TAK-041 placebo-matching suspension or tablet.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Participants and Participants with Schizophrenia: 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. 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. 3. The participant is willing to comply with study restrictions described in the protocol. 4. The participant is a healthy adult man or woman (of non-childbearing potential as described in the protocol) 5. The participant is aged 18 to 55 years, inclusive, at the time of informed consent. 6. 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. 7. 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-: 1. Is on a stable dose of an antipsychotic medication for at least 2 months as documented by medical history and assessed by site staff. 2. 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). 3. 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). 4. Has stable screening and baseline (Day -1) PANSS and NSFS total scores (less than \[\<\] 20 percent (%) change).
Exclusion criteria
Healthy Participants: 1. 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. 2. 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 3. The participant has a known hypersensitivity to any component of the formulation of TAK-041. 4. 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). 5. The participant taken any excluded medication, supplements, or food products during the time periods listed in the protocol. 6. The participant is lactose intolerant (Part3 only). 7. If female, the participant is of childbearing potential (example, premenopausal, not sterilized). 8. 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. 9. 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. 10. 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). 11. Had major surgery, or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to Screening. 12. 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. 13. 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. 14. The participant has poor peripheral venous access. 15. Had a transfusion of any blood product within 30 days prior to Day 1. 16. 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. 17. 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. 18. 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. 19. 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. 20. The participant has a clinically significant history of head injury or trauma associated with loss of consciousness for \>15 minutes. 21. 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. 22. 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: 1. Has an undetectable level of baseline antipsychotic medication at Screening. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. Has evidence of clinically significant extrapyramidal symptoms as measured by a Simson-Angus Scale (SAS) score \>6. 8. The participant has evidence of depression as measured by a Calgary Depression Score (CDSS) score \>9. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 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 |
| 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 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 |
Countries
United States
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 details
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 by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 8 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 9 |
| 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. | 9 |
| Part 4: MRD: Placebo TAK-041 placebo-matching, suspension, orally, on Days 1, 8, 15 and 22 in participants with schizophrenia | 8 |
| 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. | 16 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Voluntary Withdrawal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 40.6 years | 36.8 years | 29.3 years | 44.2 years | 42.3 years | 40.5 years | 35.5 years | 39.5 years | 38.3 years | 37.7 years | 42.5 years | 35.6 years | 34.1 years | 45.8 years | 44.3 years | 39.46 years |
| Body Mass Index (BMI) | 25.47 kg/m^2 | 25.91 kg/m^2 | 25.43 kg/m^2 | 28.36 kg/m^2 | 25.28 kg/m^2 | 28.22 kg/m^2 | 25.80 kg/m^2 | 27.63 kg/m^2 | 27.14 kg/m^2 | 25.74 kg/m^2 | 25.44 kg/m^2 | 24.76 kg/m^2 | 25.68 kg/m^2 | 30.31 kg/m^2 | 32.05 kg/m^2 | 27.24 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 4 Participants | 6 Participants | 3 Participants | 4 Participants | 7 Participants | 6 Participants | 4 Participants | 5 Participants | 4 Participants | 7 Participants | 8 Participants | 7 Participants | 15 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 176.9 cm | 174.3 cm | 171.2 cm | 175.2 cm | 164.8 cm | 178.3 cm | 178.3 cm | 174.2 cm | 168.3 cm | 173.8 cm | 173.0 cm | 175.3 cm | 175.7 cm | 173.9 cm | 174.9 cm | 174.24 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 8 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 2 Participants | 1 Participants | 3 Participants | 5 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 8 Participants | 4 Participants | 3 Participants | 5 Participants | 59 Participants |
| Region of Enrollment United States | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 9 Participants | 8 Participants | 16 Participants | 114 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 24 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 7 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 7 Participants | 8 Participants | 6 Participants | 13 Participants | 90 Participants |
| Weight | 79.68 kg | 78.63 kg | 74.43 kg | 86.97 kg | 68.52 kg | 89.83 kg | 81.79 kg | 83.40 kg | 77.20 kg | 78.22 kg | 76.43 kg | 76.07 kg | 79.42 kg | 91.46 kg | 98.58 kg | 81.82 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 8 | 0 / 16 |
| other Total, other adverse events | 4 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 2 / 6 | 2 / 6 | 2 / 6 | 3 / 8 | 4 / 6 | 4 / 6 | 3 / 6 | 5 / 6 | 1 / 9 | 2 / 9 | 6 / 8 | 9 / 16 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 8 | 0 / 16 |
Outcome results
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.
Time frame: Part 2: from first dose up to Day 66
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | ECG Mean Heart Rate, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | QRS Duration, Aggregate, <= 80 msec | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | PR Interval, Aggregate, >= 200 msec | 25.0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | ECG Mean Heart Rate, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | QRS Duration, Aggregate, <= 80 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | ECG Mean Heart Rate, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | QRS Duration, Aggregate, <= 80 msec | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | ECG Mean Heart Rate, < 50 beats/min | 50.0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | QRS Duration, Aggregate, <= 80 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | ECG Mean Heart Rate, < 50 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 2: Percentage of Participants Who Experienced Clinically Significant Abnormal Changes in Continuous 12-Lead Holter ECG Measurements at Least Once Post-Dose | QRS Duration, Aggregate, <= 80 msec | 0 percentage of participants |
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]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 41564.5 h*ng/mL | Standard Deviation 7713.08 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 45499.1 h*ng/mL | Standard Deviation 16007.58 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 37795.2 h*ng/mL | Standard Deviation 5667.55 |
Primary
Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1] | 715.4 ng/mL | Standard Deviation 192.54 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1] | 838.3 ng/mL | Standard Deviation 176.04 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-041 in RBA/Food Effect Participants [Day 1] | 648.4 ng/mL | Standard Deviation 158.67 |
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.
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Population: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | 0 percentage of participants |
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.
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Population: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 40.0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 37.5 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 50.0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 11.1 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 22.2 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 75.0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | 56.3 percentage of participants |
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.
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Population: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 20.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 10.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 20.0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 50.0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 50.0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 50.0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 50.0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 16.7 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 37.5 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 25.0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 66.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 66.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 33.3 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 11.1 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 22.2 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 11.1 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 75.0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcF Interval, Aggregate, >= 500 msec | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | ECG Mean Heart Rate, < 50 beats/min | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QTcB Interval, Aggregate, >= 500 msec | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | PR Interval, Aggregate, >= 200 msec | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for 12-Lead Electrocardiogram (ECG) Parameters at Least Once Post-dose | QRS Duration, Aggregate, <= 80 msec | 31.3 percentage of participants |
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.
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Population: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 10.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 20.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 50.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 10.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 10.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 10.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 10.0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 10.0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 50.0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 33.3 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 62.5 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 37.5 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 83.3 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 16.7 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 33.3 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 11.1 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 33.3 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 11.1 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 25.0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 25.0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 12.5 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 25.0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Supine, < 50 beats/min | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 3 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, < 50 beats/min | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 1 min Standing, < 85 mmHg | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Temperature, < 35.6 C | 31.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, 5 min Supine, < 85 mmHg | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 5 min Supine, < 50 beats/min | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, > 120 beats/min | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, Standing, > 120 beats/min | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Supine, < 85 mmHg | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, < 50 beats/min | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Systolic Blood Pressure, Standing, < 85 mmHg | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,1 min Standing,>110 mmHg | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure, 5 min Supine, < 50 mmHg | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Diastolic Blood Pressure,3 min Standing,>110 mmHg | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 1 min Standing, > 120 beats/min | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Pulse Rate, 3 min Standing, < 50 beats/min | 0 percentage of participants |
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.
Time frame: From the first dose of study drug up to 42 days after the last dose of study drug (Up to 12 weeks)
Population: Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Placebo Cohorts 1-5 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 3: TAK-041 80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 16.7 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 4: TAK-041 120 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 1 (SRD): Cohort 5: TAK-041 160 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 16.7 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 12.5 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Placebo Cohorts 1-4 | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 1: TAK-041 40/20 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 2: TAK-041 80/40 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 3: TAK-041 120/60 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 2 (MRD): Cohort 4: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 3: Relative Bioavailability (RBA)/Food Effect: Regimen A | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 11.1 percentage of participants |
| Part 3: RBA/Food Effect: Regimen B | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 11.1 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 4: MRD: Placebo | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Glucose < 50 mg/dL, < 2.8 mmol/L | 0 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Platelets, > 600 10^9 platelets/L | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Creatine Kinase, > 5 x ULN | 12.5 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Leukocytes, > 1.5 x ULN | 6.3 percentage of participants |
| Part 4: MRD: TAK-041 160/80 mg | Percentage of Participants With Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests At Least Once Post-dose | Aspartate Aminotransferase, > 3 x ULN | 6.3 percentage of participants |
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]
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] | 1662.3 h*ng/mL | Standard Deviation 390.74 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] | 2844.6 h*ng/mL | Standard Deviation 263.78 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] | 15594.9 h*ng/mL | Standard Deviation 5560.51 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] | 22471.2 h*ng/mL | Standard Deviation 4340.25 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for TAK-041 in SRD Participants [Day 1] | 21426.6 h*ng/mL | Standard Deviation 6026.07 |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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 | 6399.5 h*ng/mL | Standard Deviation 1809.44 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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 | 11955.2 h*ng/mL | Standard Deviation 1091.59 |
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]
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] | 5237.2 h*ng/mL | Standard Deviation 1107.97 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] | 9746.9 h*ng/mL | Standard Deviation 781.89 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] | 59514.3 h*ng/mL | Standard Deviation 14414.25 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] | 92784.6 h*ng/mL | Standard Deviation 13410.06 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: AUC96: Area Under the Plasma Concentration-Time Curve From Time 0 to 96 Hours for TAK-041 in SRD Participants [Day 1] | 90585.1 h*ng/mL | Standard Deviation 15742.96 |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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 | 21180.0 h*ng/mL | Standard Deviation 5680.75 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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 | 40487.8 h*ng/mL | Standard Deviation 3088.81 |
Secondary
Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1]
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1] | 283461.1 h*ng/mL | Standard Deviation 96704.07 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1] | 381403.3 h*ng/mL | Standard Deviation 208693.96 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-041 in SRD Participants [Day 1] | 395932.4 h*ng/mL | Standard Deviation 129676.19 |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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 | 122801.1 h*ng/mL | Standard Deviation 40764.68 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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 | 203288.4 h*ng/mL | Standard Deviation 39395.16 |
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]
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] | 18038.1 h*ng/mL | Standard Deviation 9735.91 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] | 44649.4 h*ng/mL | Standard Deviation 5067.39 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] | 251124.1 h*ng/mL | Standard Deviation 67210.68 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] | 344075.1 h*ng/mL | Standard Deviation 145462.41 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t for TAK-041 in SRD Participants [Day 1] | 361251.2 h*ng/mL | Standard Deviation 97096.24 |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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 | 104692.7 h*ng/mL | Standard Deviation 48397.26 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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 | 202185.0 h*ng/mL | Standard Deviation 38724.05 |
Secondary
Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1]
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] | 139.8 ng/mL | Standard Deviation 15.25 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] | 193.3 ng/mL | Standard Deviation 27.75 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] | 909.5 ng/mL | Standard Deviation 225.29 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] | 1200.0 ng/mL | Standard Deviation 147.38 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 1] | 1121.7 ng/mL | Standard Deviation 175.31 |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only | 450.5 ng/mL | Standard Deviation 90.25 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-041 in SRD Participants [Day 8], Cohorts 1 (20 mg) and 2 (40 mg) Only | 747.2 ng/mL | Standard Deviation 103.22 |
Secondary
Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1]
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1] | 284.0 hours |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1] | 208.0 hours |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in SRD Participants [Day 1] | 260.6 hours |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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 | 312.4 hours |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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 | 306.3 hours |
Secondary
Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1]
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] | 0.992 hours |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] | 1.742 hours |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] | 3.000 hours |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] | 13.017 hours |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Part 1: Tmax: Time to Reach the Cmax for TAK-041 in SRD Participants [Day 1] | 13.517 hours |
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
Time frame: Part 1: Pre-dose on Day 8 and at multiple timepoints (Up to 96 hours) post-dose
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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 | 1.992 hours |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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 | 1.583 hours |
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]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 11940.8 h*ng/mL | Standard Deviation 3052.59 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 13827.9 h*ng/mL | Standard Deviation 5143.36 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 10571.6 h*ng/mL | Standard Deviation 2643.23 |
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]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 116064.6 h*ng/mL | Standard Deviation 36590.93 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 126001.0 h*ng/mL | Standard Deviation 34652.19 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 128857.7 h*ng/mL | Standard Deviation 81053.57 |
Secondary
Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1]
Time frame: Part 3: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1] | 2.000 hours |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1] | 2.000 hours |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Part 3: Tmax: Time to Reach the Cmax for TAK-041 in RBA/Food Effect Participants [Day 1] | 1.817 hours |
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]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 9188.0 h*ng/mL | Standard Deviation 3095.87 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 14556.7 h*ng/mL | Standard Deviation 4317.73 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 22450.3 h*ng/mL | Standard Deviation 3625.16 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | 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] | 28014.6 h*ng/mL | Standard Deviation 7698.01 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | 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] | 20400.8 h*ng/mL | Standard Deviation 5096.46 |
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]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 35102.6 h*ng/mL | Standard Deviation 6612.5 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 60770.4 h*ng/mL | Standard Deviation 15609.67 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 91712.9 h*ng/mL | Standard Deviation 12328.54 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | 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] | 123645.0 h*ng/mL | Standard Deviation 29616.79 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | 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] | 90372.3 h*ng/mL | Standard Deviation 22678.03 |
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]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 55530.5 h*ng/mL | Standard Deviation 7016.3 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 99401.9 h*ng/mL | Standard Deviation 25287.6 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 147300.0 h*ng/mL | Standard Deviation 16846.42 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | 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] | 203506.2 h*ng/mL | Standard Deviation 49784.48 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | 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] | 148889.0 h*ng/mL | Standard Deviation 40389.92 |
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]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | 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] | 55530.5 h*ng/mL | Standard Deviation 7016.3 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | 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] | 99401.9 h*ng/mL | Standard Deviation 25287.6 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | 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] | 147300.0 h*ng/mL | Standard Deviation 16846.42 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | 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] | 203506.2 h*ng/mL | Standard Deviation 49784.48 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | 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] | 148889.0 h*ng/mL | Standard Deviation 40389.92 |
Secondary
Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] | 549.7 ng/mL | Standard Deviation 146.05 |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] | 879.7 ng/mL | Standard Deviation 217.95 |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] | 1260.8 ng/mL | Standard Deviation 265.22 |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] | 1760.0 ng/mL | Standard Deviation 349.69 |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Parts 2 and 4: Cmax: Maximum Observed Plasma Concentration for TAK-041 in MRD Participants [Day 1] | 1266.5 ng/mL | Standard Deviation 366.1 |
Secondary
Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] | 196.2 hours |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] | 313.1 hours |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] | 153.5 hours |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] | 263.0 hours |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Parts 2 and 4: T1/2z: Terminal Disposition Phase Half-Life for TAK-041 in MRD Participants [Day 1] | 300.1 hours |
Secondary
Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1]
Time frame: Parts 2 and 4: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (SRD): Placebo Cohorts 1-5 | Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] | 2.517 hours |
| Part 1 (SRD): Cohort 1: TAK-041 5 mg | Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] | 1.525 hours |
| Part 1 (SRD): Cohort 2: TAK-041 10 mg | Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] | 2.500 hours |
| Part 1 (SRD): Cohort 1: TAK-041 20 mg | Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] | 3.000 hours |
| Part 1 (SRD): Cohort 2: TAK-041 40 mg | Parts 2 and 4: Tmax: Time to Reach the Cmax for TAK-041 in MRD Participants [Day 1] | 2.000 hours |