CompletedNCT02461160Updated Feb 15, 2019Results posted

Phase 1, TAK-915-1001, Single-Rising Dose, Multiple-Rising Dose, Drug-Drug Interaction, Relative Bioavailability, Food Effect, and Effect on Elderly Participants Study

A Phase 1 interventional study of TAK-915 suspension and Midazolam in Healthy Volunteers, sponsored by Takeda. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-02-15.

Sponsored by Takeda · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 88
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Healthy Volunteers

Keywords

Drug therapy

In context

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
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.
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.
Weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 35.0 kg/m\^2, inclusive at Screening.
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.
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

Exclusion Criteria:

Has received any investigational compound within 30 days prior to the first dose of study medication.
Has received TAK-915 in a previous clinical study or as a therapeutic agent.
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.
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.
Has a known hypersensitivity to any component of the formulation of TAK-915 and/or midazolam.
If female, the participant is of childbearing potential (eg. premenopausal, not sterilized).
Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day 1).
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.
Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table.
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.
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.
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.
Has mental retardation or medical condition that can cause cognitive impairment.
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).
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).
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.
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).
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.
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.
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).
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).
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).
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.
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).
Has poor peripheral venous access.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 88 participants (actual)

Study arms

Placebo comparator
SRD Cohorts 1-3: Placebo
TAK-915 placebo-matching suspension, orally, once on Day 1.
Drug: TAK-915 suspension
Experimental
SRD Cohort 1 TAK-915 30 mg
TAK-915 30 mg suspension, orally, once on Day 1.
Drug: TAK-915 suspension
Experimental
SRD Cohort 2: TAK-915 100 mg
TAK-915 100 mg suspension, orally, once on Day 1.
Drug: TAK-915 suspension
Experimental
SRD Cohort 3: TAK-915 200 mg
TAK-915 200 mg suspension, orally, once on Day 1.
Drug: TAK-915 suspension
Placebo comparator
MRD Cohorts 4-6
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.
Drug: TAK-915 suspension
Experimental
MRD Cohort 4: 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.
Drug: TAK-915 suspension
Experimental
MRD Cohort 5: 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.
Drug: TAK-915 suspension
Experimental
MRD Cohort 6: 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.
Drug: TAK-915 suspension
Experimental
DDI Cohort 7: 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).
Drug: TAK-915 suspension
Experimental
BA/FE Cohort 8 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.
Drug: TAK-915 suspension
Experimental
BA/FE Cohort 9 Group 1: 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.
Drug: TAK-915 suspension · Drug: Midazolam
Experimental
BA/FE Cohort 10 Group 1: 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.
Drug: Placebo
Experimental
ESSD Cohort 11: TAK-915 50 mg
TAK-915 50 mg, suspension, orally, under fasted conditions, once on Day 1 in participants aged 65 to 75 years.
Drug: TAK-915 suspension · Drug: TAK-915 tablet

Interventions

DrugTAK-915 suspension
TAK-915 oral suspension
DrugMidazolam
Midazolam oral solution
Also known as: Versed
DrugPlacebo
Placebo-matching TAK-915 suspension
DrugTAK-915 tablet
TAK-915 tablet

What researchers measure

Primary outcomes

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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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

Secondary outcomes

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Results

Posted Feb 15, 2019

Participant flow

Participants took part in the study at 1 investigative site in the United States from 12 May 2015 01 Aug 2016.

Participant flow — Overall Study
Milestone	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
Started	8	6	6	12	6	6	6	6	12	4	4	4	8
Completed	8	6	6	12	6	6	6	5	12	4	4	4	8
Not completed	0	0	0	0	0	0	0	1	0	0	0	0	0
Withdrew: Lost to follow-up	0	0	0	0	0	0	0	1	0	0	0	0	0

Outcome measures

PrimaryPercentage 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)
Reported as:: Number · percentage of participants

Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
percentage of participants	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: Midazolam 2 mg	DDI Cohort 8: TAK-915 100 mg	DDI Cohort 8: TAK-915 + Midazolam 2 mg	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C	ESSD Cohort 12: TAK-915 50 mg
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	0	16.7	33.3	16.7	16.7	33.3	16.7	33.3	0	41.7	8.3	16.7	0	25	25

PrimaryPercentage 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)
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
percentage of participants	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: Midazolam 2 mg	DDI Cohort 8: TAK-915 100 mg	DDI Cohort 8: TAK-915 + Midazolam 2 mg	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C	ESSD Cohort 12: TAK-915 50 mg
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

PrimaryPercentage 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)
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Vital Sign Measurements
percentage of participants	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: Midazolam 2 mg	DDI Cohort 8: TAK-915 100 mg	DDI Cohort 8: TAK-915 + Midazolam 2 mg	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C	ESSD Cohort 12: TAK-915 50 mg
Standing, after 1 minute SBP, <85 mmHg	0	0	0	0	0	0	16.7	16.7	0	16.7	8.3	0	0	0	0
Standing, after 1 minutes SBP, >180 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Standing, after 3 minutes SBP(mmHg), <85 mmHg	0	0	0	8.3	0	0	16.7	0	0	16.7	0	0	0	0	0
Standing, after 3 minutes SBP, >180 mmHg	0	0	0	0	0	0	0	16.7	0	0	0	0	0	0	0
Supine, after 5 minutes SBP, <85 mmHg	0	0	16.7	0	0	0	33.3	0	0	16.7	0	16.7	8.3	8.3	0
Supine, after 5 minutes SBP, >180 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Standing, after 1 minute DBP, <50 mmHg	0	0	0	0	0	0	0	0	0	0	8.3	0	0	0	0
Standing, after 1 minute DBP, >110 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Standing, after 3 minutes DBP, <50 mmHg	0	0	0	0	0	0	16.7	0	0	8.3	0	0	0	0	0
Standing, after 3 minutes DBP, >110 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Supine, after 5 minutes DBP, <50 mmHg	12.5	0	16.7	8.3	0	0	33.3	0	8.3	0	8.3	8.3	0	0	12.5
Supine, after 5 minutes DBP, >110 mmHg	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Standing, after 1 min PR, <50 beats/min	0	0	0	0	33.3	0	16.7	0	0	0	0	0	0	0	0
Standing, after 1 min PR, >120 beats/min	0	0	0	0	0	16.7	0	33.3	0	8.3	0	0	0	8.3	0
Standing, after 3 mins PR, <50 beats/min	0	0	0	0	0	0	16.7	0	0	0	8.3	0	0	0	0
Standing, after 3 mins PR, >120 beats/min	0	16.7	0	0	0	16.7	16.7	16.7	0	8.3	8.3	8.3	0	0	0
Supine, after 5 mins PR, <50 beats/min	25	0	16.7	16.7	50	50	50	0	0	0	0	0	0	0	0
Supine, after 5 mins PR, >120 beats/min	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Standing, after 1 min Temperature, <35.6 °C	0	16.7	0	16.7	0	0	0	0	0	0	0	0	0	0	12.5
Standing, after 1 min Temperature, >37.7 °C	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Standing, after 3 mins Temperature, <35.6 °C	0	16.7	0	16.7	0	0	0	0	0	0	0	0	0	0	12.5
Standing, after 3 mins Temperature, >37.7 °C	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Supine, after 5 mins Temperature, <35.6 °C	0	16.7	0	16.7	16.7	33.3	0	16.7	0	8.3	0	0	0	8.3	12.5
Supine, after 5 mins Temperature, >37.7 °C	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

PrimaryPercentage 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)
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters
percentage of participants	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: Midazolam 2 mg	DDI Cohort 8: TAK-915 100 mg	DDI Cohort 8: TAK-915 + Midazolam 2 mg	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C	ESSD Cohort 12: TAK-915 50 mg
Heart Rate, <50 beats/min	37.5	0	16.7	25	66.7	50	50	0	0	0	0	8.3	0	0	0
Heart Rate, >120 beats/min	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
PR Interval, <=80 msec (ms)	0	0	0	0	0	0	16.7	0	0	0	0	0	0	0	0
PR Interval, >=200 ms	12.5	16.7	0	8.3	33.3	16.7	16.7	33.3	8.3	8.3	16.7	25	25	8.3	12.5
QRS Interval, <=80 ms	12.5	16.7	16.7	8.3	0	0	0	33.3	8.3	25.0	25.0	16.7	16.7	8.3	25
QRS Interval, >=180 ms	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
QT Interval, <=300 ms	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
QT Interval, >=460 ms	0	0	0	0	16.7	0	0	0	0	0	0	0	0	0	12.5
QTcB Interval, <=300 ms	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
QTcB Interval,≥500ms OR ≥450ms and ≥30ms CFB	0	0	0	0	0	0	0	16.7	0	0	0	0	8.3	0	0
QTcF Interval, <= 300 ms	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
QTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

PrimaryTmax: 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
Reported as:: Median · hr

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915
hr	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	1.750 (1.50 to 6.00)	2.000 (0.50 to 4.00)	2.000 (1.00 to 3.00)	2.508 (1.00 to 6.10)	1.500 (1.50 to 3.00)	1.500 (1.00 to 4.00)	3.058 (3.00 to 6.00)	1.500 (1.00 to 2.00)
Day 8	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	1.500 (1.50 to 2.00)	2.000 (1.50 to 4.00)	2.00 (1.50 to 3.00)	NA (NA to NA)
Day 14	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	1.500 (1.50 to 1.52)	2.500 (1.00 to 4.00)	3.000 (1.00 to 4.00)	NA (NA to NA)

PrimaryCmax: 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
Reported as:: Mean · ng/mL

Cmax: Maximum Observed Plasma Concentration for TAK-915
ng/mL	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	203.7 ± 42.77	654.8 ± 145.97	417.3 ± 96.27	675.8 ± 168.66	209.5 ± 46.60	651.8 ± 227.77	743.8 ± 148.45	414.0 ± 106.43
Day 8	NA ± NA	NA ± NA	NA ± NA	NA ± NA	196.0 ± 47.72	651.0 ± 130.51	836.7 ± 220.01	NA ± NA
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	397.5 ± 137.14	1081.0 ± 170.94	1865.0 ± 334.71	NA ± NA

PrimaryAUC(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
Reported as:: Mean · ng*hr/mL

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915
ng*hr/mL	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	2560.0 ± 631.76	8293.3 ± 1430.62	5478.1 ± 729.80	10285.1 ± 1515.01	2610.0 ± 534.55	7984.6 ± 1437.41	11640.5 ± 1889.06	4693.0 ± 637.27
Day 8	NA ± NA	NA ± NA	NA ± NA	NA ± NA	2301.7 ± 782.55	8333.9 ± 890.57	12549.3 ± 3355.02	NA ± NA
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	5688.9 ± 2759.15	15068.7 ± 2367.02	31656.0 ± 5574.82	NA ± NA

PrimaryAUClast: 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
Reported as:: Mean · ng*hr/mL

AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915
ng*hr/mL	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	5187.3 ± 956.99	18229.5 ± 5124.97	10812.4 ± 1098.50	24204.7 ± 3870.08	5380.9 ± 2065.75	15640.0 ± 2998.50	30251.6 ± 4473.58	11552.2 ± 2214.35
Day 8	NA ± NA	NA ± NA	NA ± NA	NA ± NA	2301.7 ± 782.55	8334.6 ± 890.88	12549.3 ± 3355.02	NA ± NA
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	12653.2 ± 8536.11	27924.7 ± 7330.59	67706.4 ± 22451.23	NA ± NA

PrimaryAUC∞: 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
Reported as:: Mean · ng*hr/mL

AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915
ng*hr/mL	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915	6197.1 ± 1102.70	19345.6 ± 5548.95	12198.3 ± 1312.58	30243.3 ± 7208.93	6565.6 ± 3237.81	17507.2 ± 4461.40	40326.7 ± 11260.16	16991.5 ± 4349.17

PrimaryRac(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
Reported as:: Mean · Ratio

Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915
Ratio	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg
Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915	2.100 ± 0.6568	1.973 ± 0.6523	2.761 ± 0.5207

PrimaryRac(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
Reported as:: Mean · Ratio

Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915
Ratio	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg
Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915	1.884 ± 0.4627	1.859 ± 0.7642	2.556 ± 0.5148

PrimaryTime 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
Reported as:: Mean · ratio

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
ratio	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 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	0.873 ± 0.1342	0.883 ± 0.1441	0.846 ± 0.1463

PrimaryCmax: 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
Reported as:: Mean · ng/mL

Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort
ng/mL	DDI Cohort 7: TAK-915 + Midazolam 2 mg
Day 1	9.6 ± 3.02
Day 16	8.3 ± 2.17

PrimaryAUC(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
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	DDI Cohort 7: TAK-915 + Midazolam 2 mg
Day 1	25.0 ± 10.09
Day 16	17.4 ± 5.48

PrimaryAUC(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
Reported as:: Mean · Ratio

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
Ratio	DDI Cohort 7: TAK-915 + Midazolam 2 mg
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 ± 0.1509

SecondaryTerminal 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
Reported as:: Median · hr

Terminal Elimination Half-life (t1/2) for TAK-915
hr	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	35.246 ± 42.77	34.008 ± 145.97	32.621 ± 96.27	37.826 ± 168.66	37.166 ± 46.60	23.326 ± 227.77	46.408 ± 148.45	61.244 ± 106.43
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	32.770 ± 137.14	23.517 ± 170.94	35.503 ± 334.71	NA ± NA

SecondaryCL/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
Reported as:: Mean · L/hr

CL/F: Apparent Clearance for TAK-915
L/hr	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	4.966 ± 0.8498	5.565 ± 1.7418	16.566 ± 1.9026	6.928 ± 1.5930	5.437 ± 2.3306	5.993 ± 1.3303	5.313 ± 1.6232	5.651 ± 2.3825
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	6.289 ± 2.6024	6.791 ± 1.1948	6.625 ± 1.2982	NA ± NA

SecondaryApparent 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
Reported as:: Mean · L

Apparent Volume of Distribution (Vz/F) for TAK-915
L	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	271.621 ± 81.4842	253.274 ± 44.1565	739.900 ± 138.9342	384.373 ± 54.7107	253.191 ± 43.9653	219.807 ± 44.0421	289.052 ± 33.6825	251.206 ± 28.7250
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	290.034 ± 47.4883	231.463 ± 38.5789	373.816 ± 143.239	NA ± NA

SecondaryTotal 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
Reported as:: Mean · ng

Total Amount of Drug Excreted in Urine (Ae) for TAK-915
ng	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg
Day 1	10716.238 ± 6732.8265	56307.372 ± 22847.5616	39016.323 ± 39432.2098	70789.157 ± 31812.6780	11637.538 ± 7559.7833	75873.405 ± 57990.3620	84953.950 ± 28044.2529
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	23712.223 ± 16960.3220	107635.360 ± 66665.1502	173279.223 ± 102551.0702

SecondaryFraction 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
Reported as:: Mean · fraction excreted

Fraction of Drug Excreted in Urine (Fe) for TAK-915
fraction excreted	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg
Day 1	0.036 ± 0.0224	0.056 ± 0.0228	0.020 ± 0.0197	0.035 ± 0.0159	0.039 ± 0.0252	0.076 ± 0.0580	0.042 ± 0.0140
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	0.079 ± 0.0565	0.108 ± 0.0667	0.099 ± 0.0471

SecondaryRenal 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
Reported as:: Mean · mL/hr

Renal Clearance (CLr) for TAK-915
mL/hr	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg
Day 1	2.140 ± 1.3783	3.191 ± 1.1645	3.612 ± 3.5780	2.915 ± 1.3632	2.265 ± 1.7248	5.047 ± 4.2166	2.934 ± 1.2499
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	2.208 ± 0.8706	4.696 ± 4.5467	3.246 ± 2.0065

SecondaryCmax: 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
Reported as:: Mean · ng/mL

Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort
ng/mL	DDI Cohort 7: TAK-915 + Midazolam 2 mg
Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort	519.7 ± 156.12

SecondaryAUC(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
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	DDI Cohort 7: TAK-915 + Midazolam 2 mg
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 ± 2130.73

SecondaryAUC(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
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	DDI Cohort 7: TAK-915 + Midazolam 2 mg
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 ± 5803.03

SecondaryRatio 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
Reported as:: Mean · ratio

Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts
ratio	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Day 1	0.230 ± 0.0281	0.248 ± 0.0440	0.254 ± 0.0287	0.273 ± 0.0550	0.212 ± 0.0410	0.267 ± 0.0454	0.277 ± 0.0632	0.207 ± 0.0326
Day 14	NA ± NA	NA ± NA	NA ± NA	NA ± NA	0.356 ± 0.0609	0.480 ± 0.0764	0.0764 ± 0.0690	NA ± NA

SecondaryRatio 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
Reported as:: Mean · ratio

Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts
ratio	SRD Cohort 1 TAK-915 30 mg	SRD Cohort 2: TAK-915 100 mg	SRD Cohort 3: TAK-915 200 mg	SRD Cohort 4: TAK-915 200 mg	ESSD Cohort 12: TAK-915 50 mg
Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts	0.492 ± 0.1179	0.475 ± 0.1029	0.483 ± 0.1037	0.576 ± 0.1071	0.451 ± 0.1334

SecondaryRatio 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
Reported as:: Mean · ratio

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
ratio	MRD Cohort 5: TAK-915 30 mg	MRD Cohort 6: TAK-915 100 mg	MRD Cohort 7: TAK-915 200 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	0.496 ± 0.1177	0.640 ± 0.1177	0.505 ± 0.0940

SecondaryCmax: 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
Reported as:: Mean · ng/mL

Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
ng/mL	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C
TAK-915	337.0 ± 337.0	208.0 ± 68.48	143.4 ± 55.03
Metabolite M-I	79.2 ± 18.55	48.9 ± 13.21	34.6 ± 16.03

SecondaryAUClast: 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
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C
TAK-915	8412.3 ± 2019.40	7310.0 ± 1928.95	5740.2 ± 2227.13
Metabolite M-I	3785.3 ± 771.24	2992.1 ± 582.21	2208.7 ± 888.83

SecondaryAUC(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
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C
TAK-915	10155.2 ± 2909.10	9414.5 ± 9414.5	7151.5 ± 2836.73
Metabolite M-I	4727.2 ± 1073.11	4145.2 ± 1027.33	3011.6 ± 1315.23

SecondaryTmax: 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
Reported as:: Median · hr

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
hr	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C
TAK-915	1.500 (1.00 to 3.40)	3.000 (1.50 to 6.00)	7.000 (4.08 to 24.00)
Metabolite M-I	2.250 (1.00 to 12.00)	10.000 (2.00 to 24.00)	24.000 (10.00 to 32.00)

SecondaryTerminal 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
Reported as:: Median · hr

Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
hr	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C
TAK-915	34.973 (19.83 to 52.65)	45.359 (21.43 to 63.71)	40.101 (19.46 to 53.53)
Metabolite M-I	39.937 (19.68 to 68.78)	50.010 (19.55 to 142.18)	48.406 (19.43 to 76.85)

Secondaryλz: 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
Reported as:: Mean · 1/hr

λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
1/hr	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C
TAK-915	0.0202 ± 0.00623	0.0187 ± 0.00677	0.0202 ± 0.00702
Metabolite M-I	0.0180 ± 0.00665	0.0155 ± 0.00834	0.0162 ± 0.00748

Adverse events

Collected over 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). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
SRD Cohorts Pooled Placebo	—	0/8 (0%)	0/8 (0%)
SRD Cohort 1 TAK-915 30 mg	—	0/6 (0%)	1/6 (16.7%)
SRD Cohort 2: TAK-915 100 mg	—	0/6 (0%)	2/6 (33.3%)
SRD Cohort 3: TAK-915 200 mg	—	0/12 (0%)	2/12 (16.7%)
MRD Cohorts Pooled Placebo	—	0/6 (0%)	1/6 (16.7%)
MRD Cohort 5: TAK-915 30 mg	—	0/6 (0%)	2/6 (33.3%)
MRD Cohort 6: TAK-915 100 mg	—	0/6 (0%)	1/6 (16.7%)
MRD Cohort 7: TAK-915 200 mg	—	1/6 (16.7%)	1/6 (16.7%)
DDI Cohort 8: Midazolam 2 mg	—	0/12 (0%)	0/12 (0%)
DDI Cohort 8: TAK-915 100 mg	—	0/12 (0%)	5/12 (41.7%)
DDI Cohort 8: TAK-915 + Midazolam 2 mg	—	0/12 (0%)	1/12 (8.3%)
BA/FE Cohort Regimen A	—	0/12 (0%)	2/12 (16.7%)
BA/FE Cohort Regimen B	—	0/12 (0%)	0/12 (0%)
BA/FE Cohort Regimen C	—	0/12 (0%)	3/12 (25%)
ESSD Cohort 12: TAK-915 50 mg	—	0/8 (0%)	2/8 (25%)

Most frequent serious events

Most frequent serious events
Event	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: Midazolam 2 mg	DDI Cohort 8: TAK-915 100 mg	DDI Cohort 8: TAK-915 + Midazolam 2 mg	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C	ESSD Cohort 12: TAK-915 50 mg
AnxietyNervous system disorders	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

Most frequent other events

Showing 10 of 20

Most frequent other events
Event	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: Midazolam 2 mg	DDI Cohort 8: TAK-915 100 mg	DDI Cohort 8: TAK-915 + Midazolam 2 mg	BA/FE Cohort Regimen A	BA/FE Cohort Regimen B	BA/FE Cohort Regimen C	ESSD Cohort 12: TAK-915 50 mg
DiarrhoeaGastrointestinal disorders	0/8	0/6	1/6	1/12	0/6	0/6	0/6	0/6	0/12	0/12	0/12	0/12	0/12	0/12	0/8
HeadacheNervous system disorders	0/8	0/6	0/6	2/12	0/6	0/6	0/6	0/6	0/12	0/12	0/12	0/12	0/12	0/12	1/8
Chest discomfortGeneral disorders	0/8	0/6	1/6	0/12	0/6	0/6	0/6	0/6	0/12	1/12	0/12	0/12	0/12	0/12	0/8
DizzinessNervous system disorders	0/8	1/6	0/6	0/12	0/6	0/6	0/6	0/6	0/12	0/12	0/12	0/12	0/12	0/12	0/8
PollakiuriaRenal and urinary disorders	0/8	0/6	0/6	0/12	0/6	0/6	1/6	1/6	0/12	0/12	0/12	0/12	0/12	0/12	0/8
Application site irritationGeneral disorders	0/8	0/6	0/6	0/12	1/6	1/6	0/6	0/6	0/12	2/12	0/12	0/12	0/12	0/12	0/8
Faeces hardGastrointestinal disorders	0/8	0/6	0/6	0/12	0/6	1/6	0/6	0/6	0/12	0/12	0/12	0/12	0/12	0/12	0/8
Infrequent bowel movementsGastrointestinal disorders	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
HyperhidrosisSkin and subcutaneous tissue disorders	0/8	0/6	0/6	0/12	0/6	0/6	0/6	0/6	0/12	0/12	0/12	0/12	0/12	2/12	0/8
InjuryInjury, poisoning and procedural complications	0/8	0/6	0/6	0/12	0/6	0/6	0/6	0/6	0/12	0/12	0/12	0/12	0/12	0/12	1/8

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	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
Mean	35.1 ± 9.76	37.8 ± 16.68	41.0 ± 12.47	31.9 ± 6.76	35.7 ± 11.36	33.7 ± 4.32	37.8 ± 5.74	38.7 ± 10.03	38.5 ± 8.53	35.3 ± 14.36	37.5 ± 12.34	37.5 ± 8.70	68.8 ± 2.25	39.177 (18 to 72)

Sex: Female, Male
Sex: Female, Male(Participants)	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
Female	1	1	2	2	0	0	1	1	2	2	0	2	6	20
Male	7	5	4	10	6	6	5	5	10	2	4	2	2	68

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	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
Asian	0	0	1	0	0	0	0	0	1	0	1	0	0	3
Black or African American	6	1	0	4	4	1	2	3	3	2	2	1	0	29
White	2	5	5	8	2	5	4	2	8	2	1	3	6	53
Multiracial	0	0	0	0	0	0	0	1	0	0	0	0	1	2
Native Hawaiian or other Pacific islander	0	0	0	0	0	0	0	0	0	0	0	0	1	1

Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)	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
Mean	27.6 ± 4.41	24.9 ± 5.26	26.1 ± 2.95	27.6 ± 3.99	27.4 ± 1.71	26.5 ± 3.00	24.4 ± 3.95	27.9 ± 2.52	28.2 ± 2.23	27.7 ± 6.33	27.0 ± 1.52	30.6 ± 2.93	28.2 ± 2.75	27.238 (19 to 34)

Smoking History
Smoking History(Participants)	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
Particiapnt has never smoked	6	5	6	11	5	5	4	4	10	4	3	3	7	73
Particiapnt is a current smoker	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Participant is an ex-smoker	2	1	0	1	1	1	2	2	2	0	0	1	1	14

Xanthine/caffeine history
Xanthine/caffeine history(Participants)	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
Yes	4	3	4	5	1	3	3	4	4	2	2	1	7	43
No	4	3	2	7	5	3	3	2	8	2	2	3	1	45

Study locations

1 site

Austin, Texas, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 15, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02461160
Lead sponsor: Takeda
Responsible party: Sponsor
First posted: Jun 3, 2015
Start date: May 12, 2015
Primary completion: Aug 1, 2016
Completion: Aug 1, 2016
Results posted: Feb 15, 2019
Last update: Feb 15, 2019

Study contacts

Medical Director Clinical Science

study director · Takeda

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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