Effects of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults

NCT01892189 | Completed Phase 1 Results

• 2 other identifiers: TAK-063_102U1111-1141-2177
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests.

Conditions

Ketamine-Induced Brain Activity Changes; Psychotic-like Symptoms

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Ketamine-Induced Brain Activity in Regions of Interest During Resting State

  Ketamine model was used to enhance the sensitivity to detect an effect of phosphodiesterase 10a (PDE10a) inhibition by TAK-063 by ketamine using neuroimaging battery tests. Ketamine induced robust blood oxygen level-dependent(BOLD) functional magnetic resonance imaging(fMRI) response while maintaining minimal accompanying psychotomimetic symptoms. The regions of interest include:left anterior cingulate cortex,right anterior cingulate cortex,left posterior cingulate cortex,right posterior cingulate cortex,left striatum,right striatum,left amygdala,right amygdala,left substantia nigra,right substantia nigra,left thalamus,right thalamus,left ventrolateral prefrontal cortex,right ventrolateral prefrontal cortex,left dorsolateral prefrontal cortex,right dorsolateral prefrontal cortex,left hippocampus,right hippocampus,left subgenual cingulate/Ba25,right subgenual cingulate/Ba25,left paracingulate gyrus/Ba32, and right paracingulate gyrus/Ba32.

  Day 1: 4 hours post TAK-063 dose or placebo

Secondary Outcomes (7)

• Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I)

  Day 1: pre-dose and at multiple time points (up to 24 hours) postdose

• Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I

  Day 1: pre-dose and at multiple time points (up to 24 hours) postdose

• AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 M-I

  Day 1: Pre-dose and at multiple time points (up to 24 hours) post-dose

• Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

  Baseline up to 14 days after last dose of study drug (Day 32)

• Percentage of Participants Who Meet the Takeda Global Research and Development Center, Inc. (TGRD) Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose

  Baseline up to 14 days after last dose of study drug (Day 32)

Study Arms (9)

Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg

EXPERIMENTAL

Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 milligram (mg), orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo

EXPERIMENTAL

Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg

EXPERIMENTAL

Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg

EXPERIMENTAL

Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo

EXPERIMENTAL

Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg

EXPERIMENTAL

Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg

EXPERIMENTAL

Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight: Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo

EXPERIMENTAL

Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period.

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg

EXPERIMENTAL

Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period

Drug: Ketamine; Drug: TAK-063; Drug: TAK-063 Placebo

Interventions

Ketamine DRUG

Ketamine intravenous administration.

Also known as: Ketalar™

Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg; Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo; Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg; Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg; Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo; Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg; Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg; Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo; Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg

TAK-063 DRUG

TAK-063 tablets

Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg; Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo; Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg; Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg; Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo; Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg; Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg; Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo; Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg

TAK-063 Placebo DRUG

TAK-063 placebo-matching tablets

Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg; Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo; Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg; Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg; Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo; Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg; Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg; Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo; Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator, 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.
• Is a healthy adult male.
• Speaks English as their first language.
• Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of study drug.
• Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kilogram per metre square (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.
• Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG) measurement at Screening.

You may not qualify if:

• Has received any investigational compound or ketamine within 30 days prior to Day 1 of Period 1.
• Has received TAK-063 in a previous clinical study or as a therapeutic agent.
• Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., 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 (including MRI or EEG), 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-063 or ketamine.
• Has a contraindication for ketamine.
• Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period 1).
• Has a history of drug or alcohol abuse or dependence (as defined by Diagnostic \& Statistical Manual of Mental Disorders, fourth Edition \[DSM-IV\]) within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products.
• Has evidence of current cardiovascular, central nervous system (CNS), 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-063 or ketamine 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 current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[e.g., cholecystectomy\]).
• Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1.
• Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (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, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1 of Period 1) or cotinine test is positive at Screening or Check-in (Day -1 of Period 1).
• Has poor peripheral arterial/venous access or recent wrist trauma.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

The Brain Institute, University of Utah

Salt Lake City, Utah, 84108, United States

Location

MeSH Terms

Interventions

Ketamine; 1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Medical Director
• Organization: Takeda (Note: This product was divested to Axsome in 2026)

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda Development Center Americas, Inc. (Note: This product was divested to Axsome in 2026)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: July 4, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: May 8, 2026
• Results First Posted: January 12, 2017

Record last verified: 2026-04

Locations

US (1)