Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to characterize the safety, tolerability and plasma pharmacokinetic (PK) profile of TAK-915 when administered as single and multiple oral suspension doses at escalating dose levels in healthy participants, including elderly participants.
Detailed description
The drug being tested in this study is called TAK-915. TAK-915 is being tested to find a safe and well-tolerated dose. This study will look at the pharmacokinetic characteristics (how the drug acts throughout the body) of the drug and safety and tolerability (lab results, vital signs, ECG, and side effects) in healthy people (including elderly) who take TAK-915. The study will enroll a total of 88 patients. This study is designed to consist of 5 different dosing schedules: single rising dose (SRD), multiple rising dose (MRD), drug-drug interaction (DDI), bioavailability and food effect (BA/FE), and Elderly Subject Single Dose (ESSD). The study population for SRD will consist of 48 participants enrolled into 6 cohorts. Each cohort will have 8 randomized participants, with 6 receiving a single dose of TAK-915, and 2 receiving matching placebo under fasted conditions. The starting dose is 30 mg. The dose for Cohorts 2 through 6 will be determined based on data collected from previous cohorts. The study population for MRD will consist of 32 participants enrolled into 4 cohorts. Each cohort will have 8 randomized participants, with 6 receiving one dose of TAK-915 on Day 1 and daily dosing on Days 8-14, and 2 receiving matching placebo under fasted conditions. The dose for each cohort in Part 2 will be determined based on data collected from completed SRD cohorts of the study. The study population for DDI will consist of 12 participants enrolled into 1 cohort. All participants will receive one dose of TAK-915 on Day 3 and daily dosing on Days 10-16 under fasted conditions. All participants will also receive a single dose of Midazolam 2 mg on Day 1 and Day 16. The dose of TAK-915 in this cohort will be determined based on data collected from SRD cohorts and will be the same dose that is administered in MRD Cohort 8. The study population for BA/FE will consist of 12 participants enrolled into 1 cohort. TAK-915 will be administered in 3 single-dose regimens in a 3-way crossover design using 50 mg oral dose treatments (Regimen A: TAK915 50 mg oral suspension formulation in fasted state; Regimen B: TAK-915 50 tablet formulation in fasted state; Regimen C: TAK-915 50 tablet formulation in fasted state). TAK-915 dosing will occur on Day 1 of each treatment period followed by a 14 day washout period. The study population for ESSD will consist of 8 elderly participants (ages 65-75 years) enrolled into 1 cohort. All 8 participants will receive a single dose of TAK-915 50 mg suspension under fasted conditions. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 70 days. Participants will make multiple visits to the clinic including a period of confinement to the clinic and will be contacted by telephone 12 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-915 suspension
TAK-915 oral suspension
DRUGMidazolam
Midazolam oral solution
DRUGPlacebo
Placebo-matching TAK-915 suspension
DRUGTAK-915 tablet
TAK-915 tablet
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations. 3. Is a healthy man or woman, aged 18 to 55 years, inclusive at the time of informed consent and first study medication dose for all cohorts will be included. Note that Cohort 12 will enroll healthy, elderly men and women, aged 65 to 75 years, inclusive. 4. Weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 35.0 kg/m\^2, inclusive at Screening. 5. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 6. A female participant with no childbearing potential, defined as the participant has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 y ears and follicle stimulating hormone (FSH) \>40 IU/L).
Exclusion criteria
1. Has received any investigational compound within 30 days prior to the first dose of study medication. 2. Has received TAK-915 in a previous clinical study or as a therapeutic agent. 3. 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 (eg, spouse, parent, child, sibling) or may consent under duress. 4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. 5. Has a known hypersensitivity to any component of the formulation of TAK-915 and/or midazolam. 6. If female, the participant is of childbearing potential (eg. premenopausal, not sterilized). 7. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day 1). 8. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine. 9. Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table. 10. Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study ; or intending to donate ova during such time period. 11. If male, the participant intends to donate sperm during the course of this study or for 12 weeks after the last dose of study medication. 12. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-915, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias. 13. Has mental retardation or medical condition that can cause cognitive impairment. 14. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption \[eg, bariatric surgery or bowel resection\], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent \[more than once per week\] occurrence of heartburn). 15. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Check-in (Day -1). 16. Has a positive test result for hepatitis B surface antigen (HBsAg), antibody to hepatitis C (anti -HCV) or a known history of human immunodeficiency virus infection at Screening. 17. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, electronic cigarettes, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1). Cotinine test is positive at Screening or Check-in (Day -1). 18. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior the first dose of study medication. 19. Has a Screening or Check-in (Day -1) abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved and documented by signature by the principal investigator. 20. Has a supine blood pressure outside the ranges of 90 to 140 mmHg for systolic and 60 to 90 mmHg for diastolic, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1). 21. Has a resting heart rate outside the range 40 to 100 bpm, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1). 22. Has a QT interval with Fridericia correction method (QTcF) \>430 ms (males) or \>450 ms (females) 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 (Day -1). 23. Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 the upper limits of normal. 24. Has a risk of suicide according to the Investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale \[C-SSRS\] or has made a suicide attempt in the previous 6 months). 25. Has poor peripheral venous access.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. |
| Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28) | The percentage of participants with any markedly abnormal standard safety laboratory values, including haematology, serum chemistries, or urinalysis, during the treatment period. |
| Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28) | The percentage of participants who meet markedly abnormal criteria for vital signs after dosing, including oral body temperature (temp.), respiration rate, pulse rate (PR) Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) for assessment in positions of supine or standing. Vital signs were considered abnormal if they were beyond the values defined in categories. |
| Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28) | The percentage of participants who meet markedly abnormal criteria for ECG parameters as specified by the protocol and statistical analysis plan during the treatment period. ECG parameters were considered abnormal if they were beyond the values defined in categories. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose | — |
| Cmax: Maximum Observed Plasma Concentration for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose | — |
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose | — |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose | — |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | Day 1 pre-dose and at multiple time points (up to 96 hours) post dose | — |
| Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915 | Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose | — |
| Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915 | Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose | — |
| Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1 | Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose | — |
| Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort | Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose | — |
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort | Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose | — |
| AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort | Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose |
| Terminal Elimination Half-life (t1/2) for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose |
| λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose |
| Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose |
| CL/F: Apparent Clearance for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose |
| Apparent Volume of Distribution (Vz/F) for TAK-915 | SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose |
| Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose |
| Fraction of Drug Excreted in Urine (Fe) for TAK-915 | SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose |
| Renal Clearance (CLr) for TAK-915 | SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort | Days 1 at multiple time points (up to 96 hours) post dose |
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 on Day 1 in DDI Cohort | Days 1 at multiple time points (up to 96 hours) post dose |
| AUC(0-tau): Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval Where Tau is the Length of the Dosing Interval for TAK-915 in DDI Cohort | Days 16 at multiple time points (up to 96 hours) post dose |
| Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 predose and at multiple time points (up to 96 hours) post-dose |
| Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts | Day 1 predose and at multiple time points (up to 96 hours) post-dose |
| Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts | Day 14 predose and at multiple time points (up to 96 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 12 May 2015 01 Aug 2016.
Pre-assignment details
Healthy participants were enrolled to receive TAK-915 in any of the 5 parts of the study.
Participants by arm
| Arm | Count |
|---|---|
| SRD Cohorts Pooled Placebo TAK-915 placebo-matching suspension, orally, once on Day 1. | 8 |
| SRD Cohort 1 TAK-915 30 mg TAK-915 30 mg suspension, orally, once on Day 1. | 6 |
| SRD Cohort 2: TAK-915 100 mg TAK-915 100 mg suspension, orally, once on Day 1. | 6 |
| SRD Cohort 3: TAK-915 200 mg TAK-915 200 mg suspension, orally, once on Day 1. | 12 |
| MRD Cohorts Pooled Placebo TAK-915 placebo-matching suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 placebo-matching suspension, orally, once on Days 8 to 14. | 6 |
| MRD Cohort 5: TAK-915 30 mg TAK-915 30 mg suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 30 mg suspension, orally, once on Days 8 to 14. | 6 |
| MRD Cohort 6: TAK-915 100 mg TAK-915 100 mg suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 100 mg suspension, orally, once on Days 8 to 14. | 6 |
| MRD Cohort 7: TAK-915 200 mg TAK-915 200 mg suspension, orally, once on Day 1, followed by a 7-day washout period, followed by TAK-915 200 mg suspension, orally, once on Days 8 to 14. | 6 |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg Midazolam 2 mg suspension, orally, once on Day 1, followed by TAK-915 100 mg, suspension, orally, once on Day 3, followed by a 7-day washout period, followed by TAK-915 100 mg, suspension, orally, once, daily on Days 10 to 16 and Midazolam 2 mg solution, orally, once, on Day 16 (within 15 minutes after last dose of TAK-915). | 12 |
| BA/FE Cohort 9 Group 1: A,B,C Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1, followed by Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2, followed by Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3. Each period was separated out by a 6 to 14-day washout period. | 4 |
| BA/FE Cohort 10 Group 2: B,C,A Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2, followed by Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3 followed by Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1. Each period was separated out by a 6 to 14-day washout period. | 4 |
| BA/FE Cohort 11 Group 3: C,A,B Regimen C: TAK-915 50 mg, tablet, orally under fed conditions once on Day 1 of Period 3 followed by Regimen A: TAK-915 50 mg, suspension, orally, under fasted conditions once on Day 1 of Period 1 followed by Regimen B: TAK-915 50 mg, tablet, orally, under fasted conditions once on Day 1 of Period 2. Each period was separated out by a 6 to 14-day washout period. | 4 |
| ESSD Cohort 12: TAK-915 50 mg TAK-915 50 mg, suspension, orally, under fasted conditions, once on Day 1 in participants aged 65 to 75 years. | 8 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | SRD Cohorts Pooled Placebo | SRD Cohort 1 TAK-915 30 mg | SRD Cohort 2: TAK-915 100 mg | SRD Cohort 3: TAK-915 200 mg | MRD Cohorts Pooled Placebo | MRD Cohort 5: TAK-915 30 mg | MRD Cohort 6: TAK-915 100 mg | MRD Cohort 7: TAK-915 200 mg | DDI Cohort 8: TAK-915 + Midazolam 2 mg | BA/FE Cohort 9 Group 1: A,B,C | BA/FE Cohort 10 Group 2: B,C,A | BA/FE Cohort 11 Group 3: C,A,B | ESSD Cohort 12: TAK-915 50 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.1 Years FULL_RANGE 9.76 | 37.8 Years FULL_RANGE 16.68 | 41.0 Years FULL_RANGE 12.47 | 31.9 Years FULL_RANGE 6.76 | 35.7 Years FULL_RANGE 11.36 | 33.7 Years FULL_RANGE 4.32 | 37.8 Years FULL_RANGE 5.74 | 38.7 Years FULL_RANGE 10.03 | 38.5 Years FULL_RANGE 8.53 | 35.3 Years FULL_RANGE 14.36 | 37.5 Years FULL_RANGE 12.34 | 37.5 Years FULL_RANGE 8.7 | 68.8 Years FULL_RANGE 2.25 | 39.177 Years |
| Body Mass Index (BMI) | 27.6 kg/m^2 FULL_RANGE 4.41 | 24.9 kg/m^2 FULL_RANGE 5.26 | 26.1 kg/m^2 FULL_RANGE 2.95 | 27.6 kg/m^2 FULL_RANGE 3.99 | 27.4 kg/m^2 FULL_RANGE 1.71 | 26.5 kg/m^2 FULL_RANGE 3 | 24.4 kg/m^2 FULL_RANGE 3.95 | 27.9 kg/m^2 FULL_RANGE 2.52 | 28.2 kg/m^2 FULL_RANGE 2.23 | 27.7 kg/m^2 FULL_RANGE 6.33 | 27.0 kg/m^2 FULL_RANGE 1.52 | 30.6 kg/m^2 FULL_RANGE 2.93 | 28.2 kg/m^2 FULL_RANGE 2.75 | 27.238 kg/m^2 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 1 Participants | 0 Participants | 4 Participants | 4 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 29 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 5 Participants | 5 Participants | 8 Participants | 2 Participants | 5 Participants | 4 Participants | 2 Participants | 8 Participants | 2 Participants | 1 Participants | 3 Participants | 6 Participants | 53 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 6 Participants | 20 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 4 Participants | 10 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 10 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 68 Participants |
| Smoking History Particiapnt has never smoked | 6 Participants | 5 Participants | 6 Participants | 11 Participants | 5 Participants | 5 Participants | 4 Participants | 4 Participants | 10 Participants | 4 Participants | 3 Participants | 3 Participants | 7 Participants | 73 Participants |
| Smoking History Particiapnt is a current smoker | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Smoking History Participant is an ex-smoker | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 14 Participants |
| Xanthine/caffeine history No | 4 Participants | 3 Participants | 2 Participants | 7 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 8 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 45 Participants |
| Xanthine/caffeine history Yes | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 1 / 6 | 2 / 6 | 2 / 12 | 1 / 6 | 2 / 6 | 1 / 6 | 1 / 6 | 0 / 12 | 5 / 12 | 1 / 12 | 2 / 12 | 0 / 12 | 3 / 12 | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 8 |
Outcome results
Primary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort
Time frame: Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort | Day 1 | 25.0 ng*hr/mL | Standard Deviation 10.09 |
| SRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort | Day 16 | 17.4 ng*hr/mL | Standard Deviation 5.48 |
Primary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 2560.0 ng*hr/mL | Standard Deviation 631.76 |
| SRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 1 TAK-915 30 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohort 1 TAK-915 30 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 1 TAK-915 30 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 8293.3 ng*hr/mL | Standard Deviation 1430.62 |
| SRD Cohort 2: TAK-915 100 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohort 2: TAK-915 100 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 5478.1 ng*hr/mL | Standard Deviation 729.8 |
| SRD Cohort 2: TAK-915 100 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 3: TAK-915 200 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 10285.1 ng*hr/mL | Standard Deviation 1515.01 |
| SRD Cohort 3: TAK-915 200 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 3: TAK-915 200 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | NA ng*hr/mL | — |
| MRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | 2301.7 ng*hr/mL | Standard Deviation 782.55 |
| MRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 2610.0 ng*hr/mL | Standard Deviation 534.55 |
| MRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | 5688.9 ng*hr/mL | Standard Deviation 2759.15 |
| MRD Cohort 5: TAK-915 30 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | 8333.9 ng*hr/mL | Standard Deviation 890.57 |
| MRD Cohort 5: TAK-915 30 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 7984.6 ng*hr/mL | Standard Deviation 1437.41 |
| MRD Cohort 5: TAK-915 30 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | 15068.7 ng*hr/mL | Standard Deviation 2367.02 |
| MRD Cohort 6: TAK-915 100 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | 12549.3 ng*hr/mL | Standard Deviation 3355.02 |
| MRD Cohort 6: TAK-915 100 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 11640.5 ng*hr/mL | Standard Deviation 1889.06 |
| MRD Cohort 6: TAK-915 100 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | 31656.0 ng*hr/mL | Standard Deviation 5574.82 |
| MRD Cohort 7: TAK-915 200 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 1 | 4693.0 ng*hr/mL | Standard Deviation 637.27 |
| MRD Cohort 7: TAK-915 200 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 8 | NA ng*hr/mL | — |
| MRD Cohort 7: TAK-915 200 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 | Day 14 | NA ng*hr/mL | — |
Primary
AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort
Time frame: Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort | 0.735 Ratio | Standard Deviation 0.1509 |
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 6197.1 ng*hr/mL | Standard Deviation 1102.7 |
| SRD Cohort 1 TAK-915 30 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 19345.6 ng*hr/mL | Standard Deviation 5548.95 |
| SRD Cohort 2: TAK-915 100 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 12198.3 ng*hr/mL | Standard Deviation 1312.58 |
| SRD Cohort 3: TAK-915 200 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 30243.3 ng*hr/mL | Standard Deviation 7208.93 |
| MRD Cohorts Pooled Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 6565.6 ng*hr/mL | Standard Deviation 3237.81 |
| MRD Cohort 5: TAK-915 30 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 17507.2 ng*hr/mL | Standard Deviation 4461.4 |
| MRD Cohort 6: TAK-915 100 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 40326.7 ng*hr/mL | Standard Deviation 11260.16 |
| MRD Cohort 7: TAK-915 200 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 | 16991.5 ng*hr/mL | Standard Deviation 4349.17 |
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 5187.3 ng*hr/mL | Standard Deviation 956.99 |
| SRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohort 1 TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 18229.5 ng*hr/mL | Standard Deviation 5124.97 |
| SRD Cohort 1 TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohort 1 TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 2: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 10812.4 ng*hr/mL | Standard Deviation 1098.5 |
| SRD Cohort 2: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 2: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohort 3: TAK-915 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | NA ng*hr/mL | — |
| SRD Cohort 3: TAK-915 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | NA ng*hr/mL | — |
| SRD Cohort 3: TAK-915 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 24204.7 ng*hr/mL | Standard Deviation 3870.08 |
| MRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | 12653.2 ng*hr/mL | Standard Deviation 8536.11 |
| MRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 5380.9 ng*hr/mL | Standard Deviation 2065.75 |
| MRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | 2301.7 ng*hr/mL | Standard Deviation 782.55 |
| MRD Cohort 5: TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | 8334.6 ng*hr/mL | Standard Deviation 890.88 |
| MRD Cohort 5: TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 15640.0 ng*hr/mL | Standard Deviation 2998.5 |
| MRD Cohort 5: TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | 27924.7 ng*hr/mL | Standard Deviation 7330.59 |
| MRD Cohort 6: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | 67706.4 ng*hr/mL | Standard Deviation 22451.23 |
| MRD Cohort 6: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | 12549.3 ng*hr/mL | Standard Deviation 3355.02 |
| MRD Cohort 6: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 30251.6 ng*hr/mL | Standard Deviation 4473.58 |
| MRD Cohort 7: TAK-915 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 1 | 11552.2 ng*hr/mL | Standard Deviation 2214.35 |
| MRD Cohort 7: TAK-915 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 14 | NA ng*hr/mL | — |
| MRD Cohort 7: TAK-915 200 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 | Day 8 | NA ng*hr/mL | — |
Primary
Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort
Time frame: Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort | Day 1 | 9.6 ng/mL | Standard Deviation 3.02 |
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort | Day 16 | 8.3 ng/mL | Standard Deviation 2.17 |
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 203.7 ng/mL | Standard Deviation 42.77 |
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | NA ng/mL | — |
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | NA ng/mL | — |
| SRD Cohort 1 TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 654.8 ng/mL | Standard Deviation 145.97 |
| SRD Cohort 1 TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | NA ng/mL | — |
| SRD Cohort 1 TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | NA ng/mL | — |
| SRD Cohort 2: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | NA ng/mL | — |
| SRD Cohort 2: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | NA ng/mL | — |
| SRD Cohort 2: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 417.3 ng/mL | Standard Deviation 96.27 |
| SRD Cohort 3: TAK-915 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | NA ng/mL | — |
| SRD Cohort 3: TAK-915 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 675.8 ng/mL | Standard Deviation 168.66 |
| SRD Cohort 3: TAK-915 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | NA ng/mL | — |
| MRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | 397.5 ng/mL | Standard Deviation 137.14 |
| MRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | 196.0 ng/mL | Standard Deviation 47.72 |
| MRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 209.5 ng/mL | Standard Deviation 46.6 |
| MRD Cohort 5: TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 651.8 ng/mL | Standard Deviation 227.77 |
| MRD Cohort 5: TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | 651.0 ng/mL | Standard Deviation 130.51 |
| MRD Cohort 5: TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | 1081.0 ng/mL | Standard Deviation 170.94 |
| MRD Cohort 6: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 743.8 ng/mL | Standard Deviation 148.45 |
| MRD Cohort 6: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | 836.7 ng/mL | Standard Deviation 220.01 |
| MRD Cohort 6: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | 1865.0 ng/mL | Standard Deviation 334.71 |
| MRD Cohort 7: TAK-915 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 1 | 414.0 ng/mL | Standard Deviation 106.43 |
| MRD Cohort 7: TAK-915 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 14 | NA ng/mL | — |
| MRD Cohort 7: TAK-915 200 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 | Day 8 | NA ng/mL | — |
Primary
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SRD Cohorts Pooled Placebo | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 41.7 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 8.3 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 16.7 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 25 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 25 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
The percentage of participants with any markedly abnormal standard safety laboratory values, including haematology, serum chemistries, or urinalysis, during the treatment period.
Time frame: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Safety Laboratory Tests | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters
The percentage of participants who meet markedly abnormal criteria for ECG parameters as specified by the protocol and statistical analysis plan during the treatment period. ECG parameters were considered abnormal if they were beyond the values defined in categories.
Time frame: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 12.5 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 12.5 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 37.5 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 16.7 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 16.7 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 16.7 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 16.7 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 8.3 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 25 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 8.3 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 16.7 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 66.7 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 33.3 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 16.7 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 50 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 50 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 33.3 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 33.3 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 16.7 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 8.3 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 8.3 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 25.0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 16.7 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 25.0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 16.7 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 25 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 8.3 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 8.3 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 25 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 16.7 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 8.3 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 8.3 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, <50 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval, <=300 ms | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | Heart Rate, >120 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, <= 300 ms | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, >=180 ms | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QRS Interval, <=80 ms | 25 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, <=80 msec (ms) | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, <=300 ms | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QT Interval, >=460 ms | 12.5 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | PR Interval, >=200 ms | 12.5 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
The percentage of participants who meet markedly abnormal criteria for vital signs after dosing, including oral body temperature (temp.), respiration rate, pulse rate (PR) Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) for assessment in positions of supine or standing. Vital signs were considered abnormal if they were beyond the values defined in categories.
Time frame: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)
Population: Safety set included all participants who were enrolled and received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 25 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 12.5 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 16.7 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 16.7 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 16.7 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 16.7 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 1 TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 16.7 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 16.7 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 16.7 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 2: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 16.7 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 8.3 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 16.7 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 16.7 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 16.7 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 8.3 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| SRD Cohort 3: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 33.3 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 16.7 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 50 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohorts Pooled Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 16.7 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 33.3 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 50 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 16.7 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| MRD Cohort 5: TAK-915 30 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 50 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 33.3 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 16.7 percentage of participants |
| MRD Cohort 6: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 33.3 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 16.7 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 33.3 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 16.7 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 16.7 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 16.7 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| MRD Cohort 7: TAK-915 200 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 8.3 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 16.7 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 16.7 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 100 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 16.7 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 8.3 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| DDI Cohort 8: TAK-915 + Midazolam 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 8.3 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 8.3 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 16.7 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen A | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 8.3 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen B | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 8.3 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 8.3 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 8.3 percentage of participants |
| BA/FE Cohort Regimen C | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, <50 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP(mmHg), <85 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, <50 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, >110 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, >120 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes SBP, >180 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, <85 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, >37.7 °C | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minutes SBP, >180 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins Temperature, <35.6 °C | 12.5 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, >37.7 °C | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins Temperature, <35.6 °C | 12.5 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, >110 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 mins PR, >120 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 mins PR, <50 beats/min | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, <35.6 °C | 12.5 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute SBP, <85 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes SBP, >180 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, <50 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min Temperature, >37.7 °C | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 3 minutes DBP, <50 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 minute DBP, >110 mmHg | 0 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Supine, after 5 minutes DBP, <50 mmHg | 12.5 percentage of participants |
| ESSD Cohort 12: TAK-915 50 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Standing, after 1 min PR, >120 beats/min | 0 percentage of participants |
Primary
Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915
Time frame: Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915 | 2.100 Ratio | Standard Deviation 0.6568 |
| SRD Cohort 1 TAK-915 30 mg | Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915 | 1.973 Ratio | Standard Deviation 0.6523 |
| SRD Cohort 2: TAK-915 100 mg | Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915 | 2.761 Ratio | Standard Deviation 0.5207 |
Primary
Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915
Time frame: Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915 | 1.884 Ratio | Standard Deviation 0.4627 |
| SRD Cohort 1 TAK-915 30 mg | Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915 | 1.859 Ratio | Standard Deviation 0.7642 |
| SRD Cohort 2: TAK-915 100 mg | Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915 | 2.556 Ratio | Standard Deviation 0.5148 |
Primary
Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1
Time frame: Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1 | 0.873 ratio | Standard Deviation 0.1342 |
| SRD Cohort 1 TAK-915 30 mg | Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1 | 0.883 ratio | Standard Deviation 0.1441 |
| SRD Cohort 2: TAK-915 100 mg | Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1 | 0.846 ratio | Standard Deviation 0.1463 |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | NA hr |
| SRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | NA hr |
| SRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 1.750 hr |
| SRD Cohort 1 TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | NA hr |
| SRD Cohort 1 TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | NA hr |
| SRD Cohort 1 TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 2.000 hr |
| SRD Cohort 2: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | NA hr |
| SRD Cohort 2: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | NA hr |
| SRD Cohort 2: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 2.000 hr |
| SRD Cohort 3: TAK-915 200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 2.508 hr |
| SRD Cohort 3: TAK-915 200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | NA hr |
| SRD Cohort 3: TAK-915 200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | NA hr |
| MRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | 1.500 hr |
| MRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | 1.500 hr |
| MRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 1.500 hr |
| MRD Cohort 5: TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 1.500 hr |
| MRD Cohort 5: TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | 2.500 hr |
| MRD Cohort 5: TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | 2.000 hr |
| MRD Cohort 6: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | 2.00 hr |
| MRD Cohort 6: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 3.058 hr |
| MRD Cohort 6: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | 3.000 hr |
| MRD Cohort 7: TAK-915 200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 1 | 1.500 hr |
| MRD Cohort 7: TAK-915 200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 14 | NA hr |
| MRD Cohort 7: TAK-915 200 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 | Day 8 | NA hr |
Secondary
Apparent Volume of Distribution (Vz/F) for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 271.621 L | Standard Deviation 81.4842 |
| SRD Cohorts Pooled Placebo | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | NA L | — |
| SRD Cohort 1 TAK-915 30 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 253.274 L | Standard Deviation 44.1565 |
| SRD Cohort 1 TAK-915 30 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | NA L | — |
| SRD Cohort 2: TAK-915 100 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 739.900 L | Standard Deviation 138.9342 |
| SRD Cohort 2: TAK-915 100 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | NA L | — |
| SRD Cohort 3: TAK-915 200 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 384.373 L | Standard Deviation 54.7107 |
| SRD Cohort 3: TAK-915 200 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | NA L | — |
| MRD Cohorts Pooled Placebo | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 253.191 L | Standard Deviation 43.9653 |
| MRD Cohorts Pooled Placebo | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | 290.034 L | Standard Deviation 47.4883 |
| MRD Cohort 5: TAK-915 30 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 219.807 L | Standard Deviation 44.0421 |
| MRD Cohort 5: TAK-915 30 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | 231.463 L | Standard Deviation 38.5789 |
| MRD Cohort 6: TAK-915 100 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | 373.816 L | Standard Deviation 143.239 |
| MRD Cohort 6: TAK-915 100 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 289.052 L | Standard Deviation 33.6825 |
| MRD Cohort 7: TAK-915 200 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 1 | 251.206 L | Standard Deviation 28.725 |
| MRD Cohort 7: TAK-915 200 mg | Apparent Volume of Distribution (Vz/F) for TAK-915 | Day 14 | NA L | — |
Secondary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 on Day 1 in DDI Cohort
Time frame: Days 1 at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 on Day 1 in DDI Cohort | 7324.5 ng*hr/mL | Standard Deviation 2130.73 |
Secondary
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
Time frame: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 10155.2 ng*hr/mL | Standard Deviation 2909.1 |
| SRD Cohorts Pooled Placebo | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 4727.2 ng*hr/mL | Standard Deviation 1073.11 |
| SRD Cohort 1 TAK-915 30 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 9414.5 ng*hr/mL | Standard Deviation 9414.5 |
| SRD Cohort 1 TAK-915 30 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 4145.2 ng*hr/mL | Standard Deviation 1027.33 |
| SRD Cohort 2: TAK-915 100 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 7151.5 ng*hr/mL | Standard Deviation 2836.73 |
| SRD Cohort 2: TAK-915 100 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 3011.6 ng*hr/mL | Standard Deviation 1315.23 |
Secondary
AUC(0-tau): Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval Where Tau is the Length of the Dosing Interval for TAK-915 in DDI Cohort
Time frame: Days 16 at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUC(0-tau): Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval Where Tau is the Length of the Dosing Interval for TAK-915 in DDI Cohort | 17093.9 ng*hr/mL | Standard Deviation 5803.03 |
Secondary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
Time frame: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 3785.3 ng*hr/mL | Standard Deviation 771.24 |
| SRD Cohorts Pooled Placebo | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 8412.3 ng*hr/mL | Standard Deviation 2019.4 |
| SRD Cohort 1 TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 7310.0 ng*hr/mL | Standard Deviation 1928.95 |
| SRD Cohort 1 TAK-915 30 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 2992.1 ng*hr/mL | Standard Deviation 582.21 |
| SRD Cohort 2: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 5740.2 ng*hr/mL | Standard Deviation 2227.13 |
| SRD Cohort 2: TAK-915 100 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 2208.7 ng*hr/mL | Standard Deviation 888.83 |
Secondary
CL/F: Apparent Clearance for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam. Number of participants analysed is the participants who were evaluable in each cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | CL/F: Apparent Clearance for TAK-915 | Day 14 | NA L/hr | — |
| SRD Cohorts Pooled Placebo | CL/F: Apparent Clearance for TAK-915 | Day 1 | 4.966 L/hr | Standard Deviation 0.8498 |
| SRD Cohort 1 TAK-915 30 mg | CL/F: Apparent Clearance for TAK-915 | Day 1 | 5.565 L/hr | Standard Deviation 1.7418 |
| SRD Cohort 1 TAK-915 30 mg | CL/F: Apparent Clearance for TAK-915 | Day 14 | NA L/hr | — |
| SRD Cohort 2: TAK-915 100 mg | CL/F: Apparent Clearance for TAK-915 | Day 1 | 16.566 L/hr | Standard Deviation 1.9026 |
| SRD Cohort 2: TAK-915 100 mg | CL/F: Apparent Clearance for TAK-915 | Day 14 | NA L/hr | — |
| SRD Cohort 3: TAK-915 200 mg | CL/F: Apparent Clearance for TAK-915 | Day 1 | 6.928 L/hr | Standard Deviation 1.593 |
| SRD Cohort 3: TAK-915 200 mg | CL/F: Apparent Clearance for TAK-915 | Day 14 | NA L/hr | — |
| MRD Cohorts Pooled Placebo | CL/F: Apparent Clearance for TAK-915 | Day 1 | 5.437 L/hr | Standard Deviation 2.3306 |
| MRD Cohorts Pooled Placebo | CL/F: Apparent Clearance for TAK-915 | Day 14 | 6.289 L/hr | Standard Deviation 2.6024 |
| MRD Cohort 5: TAK-915 30 mg | CL/F: Apparent Clearance for TAK-915 | Day 1 | 5.993 L/hr | Standard Deviation 1.3303 |
| MRD Cohort 5: TAK-915 30 mg | CL/F: Apparent Clearance for TAK-915 | Day 14 | 6.791 L/hr | Standard Deviation 1.1948 |
| MRD Cohort 6: TAK-915 100 mg | CL/F: Apparent Clearance for TAK-915 | Day 14 | 6.625 L/hr | Standard Deviation 1.2982 |
| MRD Cohort 6: TAK-915 100 mg | CL/F: Apparent Clearance for TAK-915 | Day 1 | 5.313 L/hr | Standard Deviation 1.6232 |
| MRD Cohort 7: TAK-915 200 mg | CL/F: Apparent Clearance for TAK-915 | Day 1 | 5.651 L/hr | Standard Deviation 2.3825 |
| MRD Cohort 7: TAK-915 200 mg | CL/F: Apparent Clearance for TAK-915 | Day 14 | NA L/hr | — |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
Time frame: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 337.0 ng/mL | Standard Deviation 337 |
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 79.2 ng/mL | Standard Deviation 18.55 |
| SRD Cohort 1 TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 208.0 ng/mL | Standard Deviation 68.48 |
| SRD Cohort 1 TAK-915 30 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 48.9 ng/mL | Standard Deviation 13.21 |
| SRD Cohort 2: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 143.4 ng/mL | Standard Deviation 55.03 |
| SRD Cohort 2: TAK-915 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 34.6 ng/mL | Standard Deviation 16.03 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort
Time frame: Days 1 at multiple time points (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort | 519.7 ng/mL | Standard Deviation 156.12 |
Secondary
Fraction of Drug Excreted in Urine (Fe) for TAK-915
Time frame: SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | NA fraction excreted | — |
| SRD Cohorts Pooled Placebo | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.036 fraction excreted | Standard Deviation 0.0224 |
| SRD Cohort 1 TAK-915 30 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | NA fraction excreted | — |
| SRD Cohort 1 TAK-915 30 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.056 fraction excreted | Standard Deviation 0.0228 |
| SRD Cohort 2: TAK-915 100 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.020 fraction excreted | Standard Deviation 0.0197 |
| SRD Cohort 2: TAK-915 100 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | NA fraction excreted | — |
| SRD Cohort 3: TAK-915 200 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.035 fraction excreted | Standard Deviation 0.0159 |
| SRD Cohort 3: TAK-915 200 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | NA fraction excreted | — |
| MRD Cohorts Pooled Placebo | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.039 fraction excreted | Standard Deviation 0.0252 |
| MRD Cohorts Pooled Placebo | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | 0.079 fraction excreted | Standard Deviation 0.0565 |
| MRD Cohort 5: TAK-915 30 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.076 fraction excreted | Standard Deviation 0.058 |
| MRD Cohort 5: TAK-915 30 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | 0.108 fraction excreted | Standard Deviation 0.0667 |
| MRD Cohort 6: TAK-915 100 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 1 | 0.042 fraction excreted | Standard Deviation 0.014 |
| MRD Cohort 6: TAK-915 100 mg | Fraction of Drug Excreted in Urine (Fe) for TAK-915 | Day 14 | 0.099 fraction excreted | Standard Deviation 0.0471 |
Secondary
Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts
Time frame: Day 14 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts | 0.496 ratio | Standard Deviation 0.1177 |
| SRD Cohort 1 TAK-915 30 mg | Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts | 0.640 ratio | Standard Deviation 0.1177 |
| SRD Cohort 2: TAK-915 100 mg | Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts | 0.505 ratio | Standard Deviation 0.094 |
Secondary
Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts
Time frame: Day 1 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts | 0.492 ratio | Standard Deviation 0.1179 |
| SRD Cohort 1 TAK-915 30 mg | Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts | 0.475 ratio | Standard Deviation 0.1029 |
| SRD Cohort 2: TAK-915 100 mg | Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts | 0.483 ratio | Standard Deviation 0.1037 |
| SRD Cohort 3: TAK-915 200 mg | Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts | 0.576 ratio | Standard Deviation 0.1071 |
| MRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts | 0.451 ratio | Standard Deviation 0.1334 |
Secondary
Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts
Time frame: Day 1 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | NA ratio | — |
| SRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.230 ratio | Standard Deviation 0.0281 |
| SRD Cohort 1 TAK-915 30 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | NA ratio | — |
| SRD Cohort 1 TAK-915 30 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.248 ratio | Standard Deviation 0.044 |
| SRD Cohort 2: TAK-915 100 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.254 ratio | Standard Deviation 0.0287 |
| SRD Cohort 2: TAK-915 100 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | NA ratio | — |
| SRD Cohort 3: TAK-915 200 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | NA ratio | — |
| SRD Cohort 3: TAK-915 200 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.273 ratio | Standard Deviation 0.055 |
| MRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.212 ratio | Standard Deviation 0.041 |
| MRD Cohorts Pooled Placebo | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | 0.356 ratio | Standard Deviation 0.0609 |
| MRD Cohort 5: TAK-915 30 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | 0.480 ratio | Standard Deviation 0.0764 |
| MRD Cohort 5: TAK-915 30 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.267 ratio | Standard Deviation 0.0454 |
| MRD Cohort 6: TAK-915 100 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.277 ratio | Standard Deviation 0.0632 |
| MRD Cohort 6: TAK-915 100 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | 0.0764 ratio | Standard Deviation 0.069 |
| MRD Cohort 7: TAK-915 200 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 14 | NA ratio | — |
| MRD Cohort 7: TAK-915 200 mg | Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts | Day 1 | 0.207 ratio | Standard Deviation 0.0326 |
Secondary
Renal Clearance (CLr) for TAK-915
Time frame: SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Renal Clearance (CLr) for TAK-915 | Day 14 | NA mL/hr | — |
| SRD Cohorts Pooled Placebo | Renal Clearance (CLr) for TAK-915 | Day 1 | 2.140 mL/hr | Standard Deviation 1.3783 |
| SRD Cohort 1 TAK-915 30 mg | Renal Clearance (CLr) for TAK-915 | Day 14 | NA mL/hr | — |
| SRD Cohort 1 TAK-915 30 mg | Renal Clearance (CLr) for TAK-915 | Day 1 | 3.191 mL/hr | Standard Deviation 1.1645 |
| SRD Cohort 2: TAK-915 100 mg | Renal Clearance (CLr) for TAK-915 | Day 14 | NA mL/hr | — |
| SRD Cohort 2: TAK-915 100 mg | Renal Clearance (CLr) for TAK-915 | Day 1 | 3.612 mL/hr | Standard Deviation 3.578 |
| SRD Cohort 3: TAK-915 200 mg | Renal Clearance (CLr) for TAK-915 | Day 1 | 2.915 mL/hr | Standard Deviation 1.3632 |
| SRD Cohort 3: TAK-915 200 mg | Renal Clearance (CLr) for TAK-915 | Day 14 | NA mL/hr | — |
| MRD Cohorts Pooled Placebo | Renal Clearance (CLr) for TAK-915 | Day 14 | 2.208 mL/hr | Standard Deviation 0.8706 |
| MRD Cohorts Pooled Placebo | Renal Clearance (CLr) for TAK-915 | Day 1 | 2.265 mL/hr | Standard Deviation 1.7248 |
| MRD Cohort 5: TAK-915 30 mg | Renal Clearance (CLr) for TAK-915 | Day 1 | 5.047 mL/hr | Standard Deviation 4.2166 |
| MRD Cohort 5: TAK-915 30 mg | Renal Clearance (CLr) for TAK-915 | Day 14 | 4.696 mL/hr | Standard Deviation 4.5467 |
| MRD Cohort 6: TAK-915 100 mg | Renal Clearance (CLr) for TAK-915 | Day 1 | 2.934 mL/hr | Standard Deviation 1.2499 |
| MRD Cohort 6: TAK-915 100 mg | Renal Clearance (CLr) for TAK-915 | Day 14 | 3.246 mL/hr | Standard Deviation 2.0065 |
Secondary
Terminal Elimination Half-life (t1/2) for TAK-915
Time frame: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 35.246 hr | Full Range 42.77 |
| SRD Cohorts Pooled Placebo | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | NA hr | — |
| SRD Cohort 1 TAK-915 30 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | NA hr | — |
| SRD Cohort 1 TAK-915 30 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 34.008 hr | Full Range 145.97 |
| SRD Cohort 2: TAK-915 100 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | NA hr | — |
| SRD Cohort 2: TAK-915 100 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 32.621 hr | Full Range 96.27 |
| SRD Cohort 3: TAK-915 200 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 37.826 hr | Full Range 168.66 |
| SRD Cohort 3: TAK-915 200 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | NA hr | — |
| MRD Cohorts Pooled Placebo | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 37.166 hr | Full Range 46.6 |
| MRD Cohorts Pooled Placebo | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | 32.770 hr | Full Range 137.14 |
| MRD Cohort 5: TAK-915 30 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 23.326 hr | Full Range 227.77 |
| MRD Cohort 5: TAK-915 30 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | 23.517 hr | Full Range 170.94 |
| MRD Cohort 6: TAK-915 100 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 46.408 hr | Full Range 148.45 |
| MRD Cohort 6: TAK-915 100 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | 35.503 hr | Full Range 334.71 |
| MRD Cohort 7: TAK-915 200 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 14 | NA hr | — |
| MRD Cohort 7: TAK-915 200 mg | Terminal Elimination Half-life (t1/2) for TAK-915 | Day 1 | 61.244 hr | Full Range 106.43 |
Secondary
Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
Time frame: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 34.973 hr |
| SRD Cohorts Pooled Placebo | Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 39.937 hr |
| SRD Cohort 1 TAK-915 30 mg | Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 50.010 hr |
| SRD Cohort 1 TAK-915 30 mg | Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 45.359 hr |
| SRD Cohort 2: TAK-915 100 mg | Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 48.406 hr |
| SRD Cohort 2: TAK-915 100 mg | Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 40.101 hr |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
Time frame: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 1.500 hr |
| SRD Cohorts Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 2.250 hr |
| SRD Cohort 1 TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 3.000 hr |
| SRD Cohort 1 TAK-915 30 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 10.000 hr |
| SRD Cohort 2: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 7.000 hr |
| SRD Cohort 2: TAK-915 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 24.000 hr |
Secondary
Total Amount of Drug Excreted in Urine (Ae) for TAK-915
Time frame: SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 10716.238 ng | Standard Deviation 6732.8265 |
| SRD Cohorts Pooled Placebo | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | NA ng | — |
| SRD Cohort 1 TAK-915 30 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 56307.372 ng | Standard Deviation 22847.5616 |
| SRD Cohort 1 TAK-915 30 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | NA ng | — |
| SRD Cohort 2: TAK-915 100 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 39016.323 ng | Standard Deviation 39432.2098 |
| SRD Cohort 2: TAK-915 100 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | NA ng | — |
| SRD Cohort 3: TAK-915 200 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 70789.157 ng | Standard Deviation 31812.678 |
| SRD Cohort 3: TAK-915 200 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | NA ng | — |
| MRD Cohorts Pooled Placebo | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 11637.538 ng | Standard Deviation 7559.7833 |
| MRD Cohorts Pooled Placebo | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | 23712.223 ng | Standard Deviation 16960.322 |
| MRD Cohort 5: TAK-915 30 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 75873.405 ng | Standard Deviation 57990.362 |
| MRD Cohort 5: TAK-915 30 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | 107635.360 ng | Standard Deviation 66665.1502 |
| MRD Cohort 6: TAK-915 100 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 1 | 84953.950 ng | Standard Deviation 28044.2529 |
| MRD Cohort 6: TAK-915 100 mg | Total Amount of Drug Excreted in Urine (Ae) for TAK-915 | Day 14 | 173279.223 ng | Standard Deviation 102551.0702 |
Secondary
λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
Time frame: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose
Population: Pharmacokinetic set included all participants who received study drug and have at least 1 measurable plasma concentration or amount of drug in the urine for either TAK-915 or its metabolite M-I or for midazolam or its metabolite 1-hydroxymidazolam.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRD Cohorts Pooled Placebo | λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 0.0202 1/hr | Standard Deviation 0.00623 |
| SRD Cohorts Pooled Placebo | λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 0.0180 1/hr | Standard Deviation 0.00665 |
| SRD Cohort 1 TAK-915 30 mg | λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 0.0187 1/hr | Standard Deviation 0.00677 |
| SRD Cohort 1 TAK-915 30 mg | λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 0.0155 1/hr | Standard Deviation 0.00834 |
| SRD Cohort 2: TAK-915 100 mg | λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | Metabolite M-I | 0.0162 1/hr | Standard Deviation 0.00748 |
| SRD Cohort 2: TAK-915 100 mg | λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort | TAK-915 | 0.0202 1/hr | Standard Deviation 0.00702 |