TAK-653 Escalating Single and Multiple Dose Study in Healthy Participants

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-26

Study Completion Date

2017-09-23

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Efficacy and Safety of TAK-653 in Treatment-Resistant Depression

NCT03312894

Treatment-Resistant Depression

WITHDRAWN PHASE2

Study to Evaluate the Efficacy and Safety of Once-Weekly Oral NBI-1065846 in the Treatment of Anhedonia in MDD

NCT05165394

Anhedonia Major Depressive Disorder

COMPLETED PHASE2

A First Time in Human Study of GSK586529 in Healthy Volunteers

NCT00703547

Depressive Disorder and Anxiety Disorders

COMPLETED PHASE1

A Safety and Tolerability Single Ascending Dose Study in Healthy Volunteers

NCT00583544

Healthy

COMPLETED PHASE1

A Study of HS-10353 in Adult Participants With Major Depressive Disorder

NCT05938179

Major Depressive Disorder (MDD)

UNKNOWN PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Depressive Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Part 1 Cohort 1: TAK-653 0.3 mg

TAK-653 0.3 milligram (mg), tablet, orally, once on Day 1 or TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 1 Cohort 2: TAK-653 1.0 mg

TAK-653 1.0 mg, tablet, orally, once on Day 1 or TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 1 Cohort 3: TAK-653 3.0 mg

TAK-653 3.0 mg, tablet, orally, once on Day 1 or TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 1 Cohort 4: TAK-653 5.0 mg

TAK-653 5.0 mg, tablet, orally, once on Day 1 or TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 1 Cohort 5: TAK-653 9.0 mg

TAK-653 9.0 mg, tablet, orally, once on Day 1 or TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 1 Cohort 6: TAK- 653 18 mg

TAK-653 18 mg, tablet, orally, once on Day 1 or TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours. Dose escalation to be decided (TBD) based on safety, tolerability, and available PK and pharmacodynamics (PD) data from previous cohorts.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 1 Additional Cohorts: TAK- 653 Placebo

TAK-653 placebo-matching tablet, orally, once on Day 1. TAK-653 or placebo will be administered after an overnight fast of approximately at least 10 hours. Dose escalation TBD based on safety, tolerability, and available PK and PD data from previous cohorts.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 2 Cohort 1: TAK-653 0.3 mg

TAK-653 0.3 mg, tablet, orally, once on Day 1, and once daily (QD) from Days 6 to 18 or placebo-matching tablet, orally, once on Day 1 and QD from Days 6 to 18.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 2 Cohort 2: TAK-653 1.0 mg

TAK-653 1.0 mg, tablet, orally, once on Day 1, and QD from Days 6 to 18 or placebo-matching tablet, orally, once on Day 1 and QD from Days 6 to 18.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 2 Cohort 3: TAK-653 3.0 mg

TAK-653 3.0 mg, tablet, orally, once on Day 1, and QD from Days 6 to 18 or placebo-matching tablet, orally, once on Day 1 and QD from Days 6 to 18.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 2 Cohort 4: TAK-653 6 mg

TAK-653 6 mg, tablet, orally, once on Day 1, and QD from Days 6 to 18 or placebo-matching tablet, orally, once on Day 1 and QD from Days 6 to 18. Dose escalation TBD based on safety, tolerability, and available PK and PD data from previous cohorts.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 2 Cohort 5: TAK-653 9 mg

TAK-653 9 mg, tablet, orally, once on Day 1, and QD from Days 6 to 18 or placebo-matching tablet, orally, once on Day 1 and QD from Days 6 to 18. Dose escalation TBD based on safety, tolerability, and available PK and PD data from previous cohorts.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Part 2 Additional Cohorts: TAK-653 Placebo

TAK-653 placebo-matching tablet, orally, once on Day 1 and QD from Days 6 to 18. Dose escalation TBD based on safety, tolerability, and available PK and PD data from previous cohorts.

Group Type EXPERIMENTAL

TAK-653 Placebo

Intervention Type DRUG

TAK-653 placebo-matching tablets.

TAK-653

Intervention Type DRUG

TAK-653 tablets.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TAK-653 Placebo

TAK-653 placebo-matching tablets.

Intervention Type DRUG

TAK-653

TAK-653 tablets.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

1. Has had CSF collected within 6 months prior to Check-in (Day -1).
2. Has a known hypersensitivity to the anesthetic or its derivatives used during CSF collection or any medication used to prepare the area of lumbar puncture.
3. Has any skin condition, abnormality of the lumbar spine, medical or surgical condition that would preclude lumbar puncture (example, coagulopathy, local or systemic infection, left ventricular outflow obstruction, aortic stenosis, raised intracranial pressure, previous back surgery).

Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes