Depressive Disorder
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of TAK-653 when administered as single and multiple oral doses at escalating dose levels in healthy participants.
Detailed description
The drug being tested in this study is called TAK-653. TAK-653 is being tested to treat people who have depression. This study will look at the tolerability and PK of TAK-653 in healthy participants. The study may enroll up to 112 participants and each cohort will enroll 8 participants. This study consists of 2 parts: Part 1- single rising dose (SRD) consisting of at least 6 cohorts and Part 2- single rising dose and multiple rising dose (SRD/MRD) consisting of at least 5 cohorts. Additional cohorts may be added depending on the emerging safety and PK data. Participants will be randomly assigned (by chance, like flipping a coin) within each cohort to receive TAK-653 or placebo which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need). Participants enrolled in Cohort 1 to 5 of Part 1 will receive TAK-653 0.3 mg, 1.0 mg, 3.0 mg, 5.0 mg and 9.0 mg or TAK-653 placebo-matching tablet. Subsequent dose escalation in Part-1, from Cohort 6 onward will occur after the full availability of safety, tolerability, PK, and PD data from preceding cohorts. Participants in Part-2 Cohorts 1 to 3 will receive TAK-653 0.3 mg, 1.0 mg and 3.0 mg respectively. Dose for Part 2, from Cohort 4 onward will be based on review of safety, tolerability, and available PK and PD data from previous cohorts. All participants will be asked to take the drug at the same time each day on Day 1 for Part 1 and Day 1 and Days 6 to 18 in Part 2. This single-center trial will be conducted in the United Kingdom. The overall time to participate in this study is approximately 14 days for Part 1 and 31 days for Part 2. Participants will be admitted to the clinic for 6 days in Part 1 and 22 days in Part 2. Participants will be followed up 14 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-653 Placebo
TAK-653 placebo-matching tablets.
DRUGTAK-653
TAK-653 tablets.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is capable of understanding and complying with protocol requirements. 2. 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 fasts for any laboratory evaluations. 3. Weighs at least 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 30.0 kilogram per square meter (kg/m\^2), inclusive at Screening. 4. 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 90 days after 5 half-lives have elapsed since last dose of study drug. This should be interpreted as 90 days from the Follow-up Call/Visit unless data indicates otherwise. 5. Female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use highly effective contraception with low user dependency from signing of informed consent, throughout the duration of the study, and for 30 days after 5 half-lives have elapsed since the last dose of study drug. This should be interpreted as 30 days from the Follow-up Call/Visit unless data indicates otherwise.
Exclusion criteria
1. Has received any investigational compound within 90 days prior to the first dose of study drug. 2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress. 3. Has any clinically significant illness, such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality, which may affect safety, increase risk of seizure or lower the seizure threshold, or potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the Takeda Medical Monitor may be warranted. 4. Has a known hypersensitivity to any component of the formulation of TAK-653. 5. Has taken any excluded medication, supplements, or food products during the time periods. 6. Is pregnant or lactating or intending to become pregnant before, during, or within 30 days after 5 half-lives have elapsed since the last dose of study drug (30 days from the Follow-up Call/Visit unless available data indicates otherwise); or intending to donate ova during such time period. 7. If male, intends to donate sperm during the course of this study or within 90 days after 5 half-lives have elapsed since the last dose of study drug. This should be interpreted as 90 days from the Follow-up Call/Visit unless data indicates otherwise. 8. Has had previous episodes of seizures or convulsion (lifetime), including absence seizure and febrile convulsion. 9. Participant or any immediate family member has a history of epilepsy (including febrile convulsions). 10. Has a history of neurological abnormalities including abnormal EEG at screening or brain injury including traumatic injury, perinatal cerebropathy and postnatal brain damage, blood-brain barrier abnormality, and angioma cavernous. 11. Has a history of cerebral arteriosclerosis. 12. Has a condition that can potentially reduce drug clearance (example, renal or hepatic insufficiency). 13. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, any surgical intervention known to impact absorption \[example, bariatric surgery or bowel resection\], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent \[more than once per week\] occurrence of heartburn). 14. 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). 15. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or a known history of human immunodeficiency virus (HIV) infection at Screening. 16. Has poor peripheral venous access. 17. Has a positive urine/blood result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1). 18. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to Screening or is unwilling to agree to abstain from alcohol and drugs throughout the study. 19. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, 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). 20. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to first dose of study drug. 21. Has a Screening or Check-in (Day -1) abnormal (clinically significant \[CS\]) ECG. Entry of any participant with an abnormal (not clinically significant \[NCS\]) ECG must be approved, and documented by signature of the principal investigator or medically qualified subinvestigator. In the case of a QT interval corrected using Fridericia's formula (QTcF) interval greater than (\>) 450 millisecond (msec) or \>480 msec (participants with Bundle Branch Block) or PR outside the range of 120 to 220 msec, assessment may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1) Visit. 22. Has a supine blood pressure outside the ranges of greater than or equal to (\>=) 90 to less than or equal to (\<=)140 millimeter of mercury (mmHg) for systolic and \>= 50 to \<= 90 mm Hg for diastolic. If out of range, assessment may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1). 23. Has a resting heart rate outside the range of 50 to 90 bpm (not on ECGs). If out of range, the assessment may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1). 24. Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a clinically significant underlying disease or participant has the following lab abnormalities: Alanine transaminase (ALT) and/or Aspartate aminotransferase (AST) \>1.5 upper limit of normal (ULN). 25. Has a risk of suicide per the C-SSRS (a score of 4 or 5 on ideation or any suicidal behavior) or according to the investigator's clinical judgment, has made a suicide attempt in the previous 6 months, or has a history of deliberate self-harm in the past 6 months. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Baseline up to Day 21 | Treatment-emergent suicidal ideation or behavior compared to baseline will be measured by an increase in suicidal ideation category (1-5 on the C-SSRS) or suicidal behavior category (6-10 on the C-SSRS) during treatment from the maximum suicidal ideation/behavior category at baseline, or any suicidal ideation/behavior during treatment if there is none at baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (1: wish to be dead; 2: non-specific active suicidal thoughts; 3: active suicidal ideation with any methods (not plan) without intent to act; 4: active suicidal ideation with some intent to act, without specific plan; 5: active suicidal ideation with specific plan and intent) and suicidal behavior (6: actual attempt; 7: interrupted attempt; 8: aborted attempt; 9: preparatory acts or behavior; 10: suicidal behavior). |
| Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | Baseline up to Day 8 | — |
| Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8 | — |
| Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | Baseline up to Day 21 | — |
| Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8 | — |
| Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | Baseline up to Day 8 | — |
| Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8 | — |
| Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | Baseline up to Day 18 | — |
| Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8 | Treatment-emergent suicidal ideation or behavior compared to baseline will be measured by an increase in suicidal ideation category (1-5 on the C-SSRS) or suicidal behavior category (6-10 on the C-SSRS) during treatment from the maximum suicidal ideation/behavior category at baseline, or any suicidal ideation/behavior during treatment if there is none at baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (1: wish to be dead; 2: non-specific active suicidal thoughts; 3: active suicidal ideation with any methods (not plan) without intent to act; 4: active suicidal ideation with some intent to act, without specific plan; 5: active suicidal ideation with specific plan and intent) and suicidal behavior (6: actual attempt; 7: interrupted attempt; 8: aborted attempt; 9: preparatory acts or behavior; 10: suicidal behavior). |
| Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Baseline up to Day 14 | — |
| Part 2: Percentage of Participants Who Experience at Least One TEAE | Baseline up to Day 31 | — |
| Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | Baseline up to Day 14 | — |
| Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | Baseline up to Day 31 | — |
| Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6 | Day 6 pre-dose at multiple timepoints (up to 24 hours) post dose |
| Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653 | Day 18 pre-dose and at multiple time points (up to 24 hours) post dose |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints up to 120 hours) post-dose |
| Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18 | Day 18 pre-dose and at multiple time points (up to 24 hours) post dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints up to 120 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints up to 120 hours) post-dose |
| Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Days 6 and 18 pre-dose and at multiple timepoints (up to 24 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints (up to 120 hours) post-dose |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in United Kingdom from 26 August 2015 to 23 September 2017.
Pre-assignment details
Healthy participants were enrolled in this 2 part study to receive TAK-653 as: single rising (SRD) dose of 0.3 milligram (mg), 1 mg, 3 mg , 5 mg, 9 mg or 18 mg in Part 1, and SRD/multiple rising dose (MRD) of 0.3 mg, 1 mg, 3 mg, 6 mg or 9 mg in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo TAK-653 placebo-matching tablet, orally, once under fasted conditions on Day 1. | 12 |
| Part 1 Cohort 1: TAK-653 0.3 mg TAK-653 0.3 mg, tablet, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 2: TAK-653 1 mg TAK-653 1 mg, tablet, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg TAK-653 3 mg, tablet, orally, once, under fasted condition on Day 1 of Period 1 and TAK-653 3 mg, tablet, orally, once, under fed condition on Day 1 of Period 2. | 6 |
| Part 1 Cohort 4: TAK-653 5 mg TAK-653 5 mg, tablet, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 5: TAK-653 9 mg TAK-653 9 mg, tablet, orally, once under fasted conditions on Day 1. | 6 |
| Part 1 Cohort 6: TAK-653 18 mg TAK-653 18 mg, tablet, orally, once under fasted conditions on Day 1. | 6 |
| Part 2 Cohorts 1-5: Pooled Placebo TAK-653 placebo-matching tablet, orally, once under fasted conditions on Day 1 and Days 6-18. | 10 |
| Part 2 Cohort 1: TAK-653 0.3 mg TAK-653 0.3 mg, tablet, orally, once under fasted conditions on Day 1 and Days 6-18. | 6 |
| Part 2 Cohort 2: TAK-653 1 mg TAK-653 1 mg, tablet, orally, once under fasted conditions on Day 1 and Days 6-18. | 6 |
| Part 2 Cohort 3: TAK-653 3 mg TAK-653 3 mg, tablet, orally, once under fasted conditions on Day 1 and Days 6-18. | 6 |
| Part 2 Cohort 4: TAK-653 6 mg TAK-653 6 mg, tablet, orally, once under fasted conditions on Day 1 and Days 6-18. | 6 |
| Part 2 Cohort 5: TAK-653 9 mg TAK-653 9 mg, tablet, orally, once under fasted conditions on Day 1 and Days 6-18. | 6 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1 Cohorts 1-6: Pooled Placebo | Total | Part 2 Cohort 5: TAK-653 9 mg | Part 2 Cohort 4: TAK-653 6 mg | Part 2 Cohort 3: TAK-653 3 mg | Part 2 Cohort 2: TAK-653 1 mg | Part 2 Cohort 1: TAK-653 0.3 mg | Part 2 Cohorts 1-5: Pooled Placebo | Part 1 Cohort 6: TAK-653 18 mg | Part 1 Cohort 5: TAK-653 9 mg | Part 1 Cohort 4: TAK-653 5 mg | Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1 Cohort 2: TAK-653 1 mg | Part 1 Cohort 1: TAK-653 0.3 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 88 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Caffeine Consumption Had caffeine consumption | 8 Participants | 66 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 9 Participants | 5 Participants | 6 Participants | 5 Participants | 4 Participants | 3 Participants | 6 Participants |
| Caffeine Consumption Had no caffeine consumption | 4 Participants | 22 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 85 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Female Reproductive Status Female of childbearing potential | 1 Participants | 3 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 |
| Female Reproductive Status Surgically sterile | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 8 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 69 Participants | 4 Participants | 6 Participants | 5 Participants | 4 Participants | 4 Participants | 7 Participants | 5 Participants | 4 Participants | 6 Participants | 6 Participants | 4 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 12 Participants | 88 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 4 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 |
| Sex: Female, Male Male | 10 Participants | 84 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants |
| Smoking Classification Ex-smoker | 2 Participants | 26 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants |
| Smoking Classification Never smoked | 10 Participants | 62 Participants | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 4 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 12 | 4 / 6 | 4 / 6 | 3 / 6 | 5 / 6 | 2 / 6 | 2 / 6 | 5 / 10 | 3 / 6 | 3 / 6 | 6 / 6 | 2 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
Treatment-emergent suicidal ideation or behavior compared to baseline will be measured by an increase in suicidal ideation category (1-5 on the C-SSRS) or suicidal behavior category (6-10 on the C-SSRS) during treatment from the maximum suicidal ideation/behavior category at baseline, or any suicidal ideation/behavior during treatment if there is none at baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (1: wish to be dead; 2: non-specific active suicidal thoughts; 3: active suicidal ideation with any methods (not plan) without intent to act; 4: active suicidal ideation with some intent to act, without specific plan; 5: active suicidal ideation with specific plan and intent) and suicidal behavior (6: actual attempt; 7: interrupted attempt; 8: aborted attempt; 9: preparatory acts or behavior; 10: suicidal behavior).
Time frame: Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 participants |
Primary
Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE)
Time frame: Baseline up to Day 14
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) | 0 percentage of participants |
Primary
Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: Baseline up to Day 14
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 41.7 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 66.7 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 50.0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 83.3 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 33.3 percentage of participants |
Primary
Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose
Time frame: Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety Electroencephalogram (EEG) Measurements at Least Once Postdose | 0 percentage of participants |
Primary
Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose
Time frame: Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 66.7 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 33.3 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 33.3 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 50.0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 33.3 percentage of participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) at Least Once Postdose | 50 percentage of participants |
Primary
Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose
Time frame: Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 16.7 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 16.7 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
Primary
Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose
Time frame: Cohort 1-5: Baseline up to Day 7; Cohort 6: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 75.0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 50.0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 100.0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 66.7 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 83.3 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 83.3 percentage of participants |
| Part 1 Cohort 6: TAK-653 18 mg | Part 1: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 66.7 percentage of participants |
Primary
Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS
Treatment-emergent suicidal ideation or behavior compared to baseline will be measured by an increase in suicidal ideation category (1-5 on the C-SSRS) or suicidal behavior category (6-10 on the C-SSRS) during treatment from the maximum suicidal ideation/behavior category at baseline, or any suicidal ideation/behavior during treatment if there is none at baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (1: wish to be dead; 2: non-specific active suicidal thoughts; 3: active suicidal ideation with any methods (not plan) without intent to act; 4: active suicidal ideation with some intent to act, without specific plan; 5: active suicidal ideation with specific plan and intent) and suicidal behavior (6: actual attempt; 7: interrupted attempt; 8: aborted attempt; 9: preparatory acts or behavior; 10: suicidal behavior).
Time frame: Baseline up to Day 21
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | 0 participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | 0 participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | 0 participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | 0 participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | 0 participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | 0 participants |
Primary
Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE
Time frame: Baseline up to Day 31
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | 0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | 0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | 0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | 0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | 16.7 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Percentage of Participants Who Discontinued the Treatment Due to an AE | 0 percentage of participants |
Primary
Part 2: Percentage of Participants Who Experience at Least One TEAE
Time frame: Baseline up to Day 31
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Percentage of Participants Who Experience at Least One TEAE | 50.0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Percentage of Participants Who Experience at Least One TEAE | 50.0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Percentage of Participants Who Experience at Least One TEAE | 50.0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Percentage of Participants Who Experience at Least One TEAE | 100.0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Percentage of Participants Who Experience at Least One TEAE | 33.3 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Percentage of Participants Who Experience at Least One TEAE | 50.0 percentage of participants |
Primary
Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose
Time frame: Baseline up to Day 18
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Percentage of Participants Who Experience Clinically Significant Abnormal Changes in Safety EEG Measurements at Least Once Postdose | 0 percentage of participants |
Primary
Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose
Time frame: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | 40.0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | 50.0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | 50.0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | 16.7 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | 50.0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety ECG at Least Once Postdose | 16.7 percentage of participants |
Primary
Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose
Time frame: Baseline up to Day 8
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 33.3 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 0 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose | 16.7 percentage of participants |
Primary
Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose
Time frame: Baseline up to Day 21
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 90.0 percentage of participants |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 100.0 percentage of participants |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 100.0 percentage of participants |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 100.0 percentage of participants |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 83.3 percentage of participants |
| Part 1 Cohort 5: TAK-653 9 mg | Part 2: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose | 83.3 percentage of participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653
Time frame: Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints up to 120 hours) post-dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 143.6521 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Part 1 Cohort 1: TAK-653 0.3 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 596.5323 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Part 1 Cohort 2: TAK-653 1 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 1419.4306 ng*hr/mL | Geometric Coefficient of Variation 26 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 2536.8525 ng*hr/mL | Geometric Coefficient of Variation 35 |
| Part 1 Cohort 4: TAK-653 5 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 4932.8519 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Part 1 Cohort 5: TAK-653 9 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 8413.1768 ng*hr/mL | Geometric Coefficient of Variation 40 |
| Part 1 Cohort 6: TAK-653 18 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 129.5373 ng*hr/mL | Geometric Coefficient of Variation 26 |
| Part 2 Cohort 2: TAK-653 1 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 448.9862 ng*hr/mL | Geometric Coefficient of Variation 36 |
| Part 2 Cohort 3: TAK-653 3 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 1773.6365 ng*hr/mL | Geometric Coefficient of Variation 40 |
| Part 2 Cohort 4: TAK-653 6 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 2027.7989 ng*hr/mL | Geometric Coefficient of Variation 56 |
| Part 2 Cohort 5: TAK-653 9 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-653 | 5066.5536 ng*hr/mL | Geometric Coefficient of Variation 69 |
Secondary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653
Time frame: Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints up to 120 hours) post-dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 122.9927 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| Part 1 Cohort 1: TAK-653 0.3 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 539.0930 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| Part 1 Cohort 2: TAK-653 1 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 1310.5344 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 2247.5468 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| Part 1 Cohort 4: TAK-653 5 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 4264.3612 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Part 1 Cohort 5: TAK-653 9 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 7755.4570 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| Part 1 Cohort 6: TAK-653 18 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 115.5869 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 22 |
| Part 2 Cohort 2: TAK-653 1 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 382.2871 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Part 2 Cohort 3: TAK-653 3 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 1417.0994 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Part 2 Cohort 4: TAK-653 6 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 1810.5437 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 42 |
| Part 2 Cohort 5: TAK-653 9 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-653 | 4065.9350 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1
Time frame: Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints (up to 120 hours) post-dose
Population: The pharmacokinetics (PK) analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 3.5985 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 14 |
| Part 1 Cohort 1: TAK-653 0.3 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 10.2220 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| Part 1 Cohort 2: TAK-653 1 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 26.9733 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 44.9430 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| Part 1 Cohort 4: TAK-653 5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 68.8039 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16 |
| Part 1 Cohort 5: TAK-653 9 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 123.6462 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| Part 1 Cohort 6: TAK-653 18 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 2.8630 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Part 2 Cohort 2: TAK-653 1 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 7.7786 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12 |
| Part 2 Cohort 3: TAK-653 3 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 28.0546 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Part 2 Cohort 4: TAK-653 6 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 41.0028 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Part 2 Cohort 5: TAK-653 9 mg | Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 1 | 76.0656 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
Secondary
Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653
Time frame: Days 6 and 18 pre-dose and at multiple timepoints (up to 24 hours) post-dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine. The PK analysis population where data at specified time points was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 6 | 51.0759 ng*hr/mL | Geometric Coefficient of Variation 19 |
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 18 | 144.7834 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 6 | 159.9789 ng*hr/mL | Geometric Coefficient of Variation 16 |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 18 | 477.3427 ng*hr/mL | Geometric Coefficient of Variation 38 |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 6 | 578.9157 ng*hr/mL | Geometric Coefficient of Variation 26 |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 18 | 1901.4065 ng*hr/mL | Geometric Coefficient of Variation 24 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 18 | 2747.5976 ng*hr/mL | Geometric Coefficient of Variation 42 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 6 | 778.2945 ng*hr/mL | Geometric Coefficient of Variation 13 |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 6 | 1485.5059 ng*hr/mL | Geometric Coefficient of Variation 39 |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-653 | Day 18 | 4144.0176 ng*hr/mL | Geometric Coefficient of Variation 60 |
Secondary
Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6
Time frame: Day 6 pre-dose at multiple timepoints (up to 24 hours) post dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6 | 3.0485 ng/mL | Geometric Coefficient of Variation 11 |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6 | 9.9202 ng/mL | Geometric Coefficient of Variation 16 |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6 | 33.4862 ng/mL | Geometric Coefficient of Variation 31 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6 | 49.2842 ng/mL | Geometric Coefficient of Variation 21 |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Cmax: Maximum Observed Plasma Concentration for TAK-653 on Day 6 | 78.8995 ng/mL | Geometric Coefficient of Variation 32 |
Secondary
Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653
Time frame: Day 18 pre-dose and at multiple time points (up to 24 hours) post dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine. The PK analysis population where data at specified time points was available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653 | 7.6221 ng/mL | Geometric Coefficient of Variation 29 |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653 | 23.9972 ng/mL | Geometric Coefficient of Variation 31 |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653 | 97.2781 ng/mL | Geometric Coefficient of Variation 28 |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653 | 140.4824 ng/mL | Geometric Coefficient of Variation 37 |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-653 | 223.3637 ng/mL | Geometric Coefficient of Variation 53 |
Secondary
Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18
Time frame: Day 18 pre-dose and at multiple time points (up to 24 hours) post dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine. The PK analysis population where data at specified time points was available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18 | 2.500 hours |
| Part 1 Cohort 1: TAK-653 0.3 mg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18 | 4.500 hours |
| Part 1 Cohort 2: TAK-653 1 mg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18 | 4.000 hours |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18 | 3.050 hours |
| Part 1 Cohort 4: TAK-653 5 mg | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 18 | 3.000 hours |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1
Time frame: Part 1 Cohort 1-5: Day 1 pre-dose and at multiple timepoints (up to 144 hours) post-dose; Part 1 Cohort 6: Day 1 pre-dose and at multiple timepoints (up to 168 hours) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints up to 120 hours) post-dose
Population: The PK analysis set included all participants who received study drug and had at least 1 measurable plasma concentration or amount of drug in urine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohorts 1-6: Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 1.250 hours |
| Part 1 Cohort 1: TAK-653 0.3 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 2.500 hours |
| Part 1 Cohort 2: TAK-653 1 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 1.750 hours |
| Part 1 Cohort 3: TAK-653 3 mg+TAK-653 3mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 2.750 hours |
| Part 1 Cohort 4: TAK-653 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 5.500 hours |
| Part 1 Cohort 5: TAK-653 9 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 5.050 hours |
| Part 1 Cohort 6: TAK-653 18 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 1.250 hours |
| Part 2 Cohort 2: TAK-653 1 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 4.000 hours |
| Part 2 Cohort 3: TAK-653 3 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 1.500 hours |
| Part 2 Cohort 4: TAK-653 6 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 5.000 hours |
| Part 2 Cohort 5: TAK-653 9 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-653 on Day 1 | 4.508 hours |